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Sample records for botulinum toxin serotype

  1. Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes.

    Science.gov (United States)

    Hill, Karen K; Smith, Theresa J

    2013-01-01

    Clostridium botulinum is a species of spore-forming anaerobic bacteria defined by the expression of any one or two of seven serologically distinct botulinum neurotoxins (BoNTs) designated BoNT/A-G. This Gram-positive bacterium was first identified in 1897 and since then the paralyzing and lethal effects of its toxin have resulted in the recognition of different forms of the intoxication known as food-borne, infant, or wound botulism. Early microbiological and biochemical characterization of C. botulinum isolates revealed that the bacteria within the species had different characteristics and expressed different toxin types. To organize the variable bacterial traits within the species, Group I-IV designations were created. Interestingly, it was observed that isolates within different Groups could express the same toxin type and conversely a single Group could express different toxin types. This discordant phylogeny between the toxin and the host bacteria indicated that horizontal gene transfer of the toxin was responsible for the variation observed within the species. The recent availability of multiple C. botulinum genomic sequences has offered the ability to bioinformatically analyze the locations of the bont genes, the composition of their toxin gene clusters, and the genes flanking these regions to understand their variation. Comparison of the genomic sequences representing multiple serotypes indicates that the bont genes are not in random locations. Instead the analyses revealed specific regions where the toxin genes occur within the genomes representing serotype A, B, C, E, and F C. botulinum strains and C. butyricum type E strains. The genomic analyses have provided evidence of horizontal gene transfer, site-specific insertion, and recombination events. These events have contributed to the variation observed among the neurotoxins, the toxin gene clusters and the bacteria that contain them, and has supported the historical microbiological, and biochemical

  2. Botulinum toxin

    Directory of Open Access Journals (Sweden)

    Nigam P

    2010-01-01

    Full Text Available Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C 1 , C 2 , D, E, F and G. All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. The weakness induced by injection with botulinum toxin A usually lasts about three months. Botulinum toxins now play a very significant role in the management of a wide variety of medical conditions, especially strabismus and focal dystonias, hemifacial spasm, and various spastic movement disorders, headaches, hypersalivation, hyperhidrosis, and some chronic conditions that respond only partially to medical treatment. The list of possible new indications is rapidly expanding. The cosmetological applications include correction of lines, creases and wrinkling all over the face, chin, neck, and chest to dermatological applications such as hyperhidrosis. Injections with botulinum toxin are generally well tolerated and side effects are few. A precise knowledge and understanding of the functional anatomy of the mimetic muscles is absolutely necessary to correctly use botulinum toxins in clinical practice.

  3. Hemagglutinin gene shuffling among Clostridium botulinum serotypes C and D yields distinct sugar recognition of the botulinum toxin complex.

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    Miyata, Keita; Suzuki, Tomonori; Hayashi, Shintaro; Miyashita, Shin-Ichiro; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro; Sagane, Yoshimasa

    2015-10-01

    Clostridium botulinum strains produce a large-sized toxin complex (TC) that is composed of botulinum neurotoxin (BoNT), non-toxic non-hemagglutinin and three different hemagglutinins (HA-70, HA-33 and HA-17). HA components enhance toxin delivery across the intestinal cell wall in a sugar chain-dependent manner. Here we characterized the sugar recognition of serotype D strain 1873 (D-1873) botulinum L-TC. Most L-TCs produced by serotype C and D strains bind to cells via interactions between HA-33 and cell surface sialo-oligosaccharides. However, like the previously reported L-TC produced by serotype C strain Yoichi (C-Yoichi), D-1873 L-TC binds only to cells that have been treated with neuraminidase, indicating that they recognize asialo-oligosaccharides. The D-1873 HA-33 amino acid sequence is similar to that of C-Yoichi, but had lower similarity to the majority of serotype C and D HA-33s. A comparison of TC component primary structures for 12 serotype C and D strains suggested that at least three types of HA-33 genes exist, and these are shuffled among the serotype C and D strains independently of BoNT serotype. This shuffling produces the distinct sugar recognition of serotype C and D botulinum TCs.

  4. A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food

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    Larry H. Stanker

    2013-11-01

    Full Text Available Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT, produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A–H have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D., ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule and readily detects toxin in those food samples tested.

  5. Construction of "Toxin Complex" in a Mutant Serotype C Strain of Clostridium botulinum Harboring a Defective Neurotoxin Gene.

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    Suzuki, Tomonori; Nagano, Thomas; Niwa, Koichi; Uchino, Masataka; Tomizawa, Motohiro; Sagane, Yoshimasa; Watanabe, Toshihiro

    2017-01-01

    A non-toxigenic mutant of the toxigenic serotype C Clostridium botulinum strain Stockholm (C-St), C-N71, does not produce the botulinum neurotoxin (BoNT). However, the original strain C-St produces botulinum toxin complex, in which BoNT is associated with non-toxic non-hemagglutinin (NTNHA) and three hemagglutinin proteins (HA-70, HA-33, and HA-17). Therefore, in this study, we aimed to elucidate the effects of bont gene knockout on the formation of the "toxin complex." Nucleotide sequence analysis revealed that a premature stop codon was introduced in the bont gene, whereas other genes were not affected by this mutation. Moreover, we successfully purified the "toxin complex" produced by C-N71. The "toxin complex" was identified as a mixture of NTNHA/HA-70/HA-17/HA-33 complexes with intact NTNHA or C-terminally truncated NTNHA, without BoNT. These results indicated that knockout of the bont gene does not affect the formation of the "toxin complex." Since the botulinum toxin complex has been shown to play an important role in oral toxin transport in the human and animal body, a non-neurotoxic "toxin complex" of C-N71 may be valuable for the development of an oral drug delivery system.

  6. [Intoxication of botulinum toxin].

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    Chudzicka, Aleksandra

    2015-09-01

    Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon.

  7. Botulinum Toxin (Botox) for Facial Wrinkles

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    ... Stories Español Eye Health / Eye Health A-Z Botulinum Toxin (Botox) for Facial Wrinkles Sections Botulinum Toxin (Botox) ... Facial Wrinkles How Does Botulinum Toxin (Botox) Work? Botulinum Toxin (Botox) for Facial Wrinkles Written by: Kierstan Boyd ...

  8. SiMa Cells for a Serotype Specific and Sensitive Cell-Based Neutralization Test for Botulinum Toxin A and E

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    Nicola Bak

    2017-07-01

    Full Text Available Botulinum toxins (BoNTs, of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay.

  9. Botulinum Neurotoxin Serotypes Detected by Electrochemical Impedance Spectroscopy

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    Savage, Alison C.; Buckley, Nicholas; Halliwell, Jennifer; Gwenin, Christopher

    2015-01-01

    Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A–E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins. PMID:25954998

  10. Botulinum Neurotoxin Serotypes Detected by Electrochemical Impedance Spectroscopy

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    Alison C. Savage

    2015-05-01

    Full Text Available Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A–E using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins.

  11. Detection of botulinum neurotoxin serotype B at sub mouse LD(50 levels by a sandwich immunoassay and its application to toxin detection in milk.

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    Miles C Scotcher

    Full Text Available BACKGROUND: Botulinum neurotoxin (BoNT, the causative agent of botulism, a serious neuroparylatic disease, is produced by the anaerobic bacterium Clostridium botulinum and consists of a family of seven serotypes (A-H. We previously reported production of high-affinity monoclonal antibodies to BoNT serotype A. METHODS AND FINDINGS: Recombinant peptide fragments of the light chain, the transmembrane and receptor-binding domains of the heavy chain of botulinum neurotoxin type B (BoNT/B were expressed in Escherichia coli as GST-fusion proteins and purified. These proteins were used to immunize BALB/cJ mice for the generation of monoclonal antibodies (mAbs. Antibody-producing hybridomas were detected using either a direct binding ELISA binding to plate-immobilized BoNT/B, or with a capture-capture ELISA whereby the capacity of the antibody to capture BoNT/B from solution was tested. A total of five mAbs were selected, two of which bound the toxin light chain and three bound the receptor-binding domain of BoNT/B heavy chain. MAb MCS6-27 was identified via capture-capture ELISA and was the only mAb able to bind BoNT/B in solution under physiological conditions. MAbs F24-1, F26-16, F27-33 and F29-40 were identified via direct binding ELISA, and were able to capture BoNT/B in solution only in the presence of 0.5-0.9 mM sodium dodecyl sulphate (SDS. MAb MCS6-27 and an anti-BoNT/B polyclonal antibody were incorporated into a sandwich ELISA that did not require SDS. CONCLUSIONS: We report here the generation of monoclonal antibodies to serotype B and the subsequent development of a sensitive sandwich immunoassay. This immunoassay has a detection limit of 100 fg BoNT/B, fifty times more sensitive than the mouse bioassay detection limit of 5 pg BoNT/B. Additionally, this assay detected as little as 39 pg/mL of toxin in skim, 2% and whole milk.

  12. Botulinum toxin: yesterday, today, tomorrow

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    A. R. Artemenko

    2013-01-01

    Full Text Available Botulinum toxin (BoNT is a bacterial neurotoxin presented with seven serotypes that inhibit neurotransmitter release from nerve endings. The serotypes of BoNT are antigenically dissimilar, act via different, but interconnected mechanisms, and are not interchangeable. The activity of BoNT is associated with impaired neuroexocytosis occurring in several steps: from the binding of BoNT to its specific receptor on the axon terminal membrane to the proteolytic enzymatic cleavage of SNARE substrate. The effect of BoNT is considered to be restricted to the peripheral nervous system, but when given in particularly high doses, it has been recently shown to affect individual brain structures. In addition, by modulating peripheral afferentation, BoNT may influence the excitability of central neuronal structures at both spinal and cortical levels. Only BoNT serotypes A and B are used in clinical practice and aesthetic medicine. The type A has gained the widest acceptance as a therapeutic agent for more than 100 abnormalities manifesting themselves as muscular hyperactivity, hyperfunction of endocrine gland, and chronic pain. The effect of BoNT preparations shows itself 2-5 days after injection, lasts 3 months or more, and gradually decreases with as a result of pharmacokinetic and intracellular reparative processes. Biotechnology advances and potentialities allow purposefully modification of the protein molecular structure of BoNT, which expands the use and efficiency of performed therapy with neurotoxins. Recombinant technologies provide a combination of major therapeutic properties of each used BoNT serotype and expand indications for recombinant chimeric toxins.

  13. Botulinum toxin: bioweapon & magic drug.

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    Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

    2010-11-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

  14. Botulinum Toxin in Pediatric Neurology

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    Eman M. I. Moawad MD

    2015-06-01

    Full Text Available Botulinum neurotoxins are natural molecules produced by anaerobic spore-forming bacteria called Clostradium boltulinum. The toxin has a peculiar mechanism of action by preventing the release of acetylcholine from the presynaptic membrane. Consequently, it has been used in the treatment of various neurological conditions related to muscle hyperactivity and/or spasticity. Also, it has an impact on the autonomic nervous system by acting on smooth muscle, leading to its use in the management of pain syndromes. The use of botulinum toxin in children separate from adults has received very little attention in the literature. This review presents the current data on the use of botulinum neurotoxin to treat various neurological disorders in children.

  15. Botulinum Toxin; Bioterror and Biomedicinal Agent

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    Jiri Patocka

    2006-04-01

    Full Text Available Botulinum toxin is a group of seven homologous, highly poisonous proteins isolated fromfermentation of the anaerobic bacterium Clostridium botulinum, which naturally occurs in soiland can grow on many meats and vegetables. Botulinum toxin causes neuromuscular disordercalled botulism, which is a potentially lethal disease. There are three types of botulism: Food,wound, and infant botulism. It can lead to death unless appropriate therapy is done. Due to theseverity and potency of botulinum toxin, its importance as a biological weapon is of majorconcern to public health officials. Nevertheless, botulinum toxin is also medicament.

  16. Expression, purification and development of neutralizing antibodies from synthetic BoNT/B LC and its application in detection of botulinum toxin serotype B.

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    Ponmariappan, S; Jain, Swati; Sijoria, Richa; Tomar, Arvind; Kumar, Om

    2012-03-01

    Botulism is a neuroparalytic disease caused by Clostridium botulinum, which produces seven (A-G) neurotoxins (BoNTs). The mouse bioassay is the gold standard for the detection of botulinum neurotoxins, however it requires at least 3-4 days for completion. Most of the studies were carried out in botulinum toxin A and less on type B. Attempts have been made to develop an ELISA based detection system, which is potentially an easier and more rapid method of botulinum neurotoxin detection. In the present study, the synthetic BoNT/B LC gene was constructed using PCR overlapping primers, cloned in a pET28a+ vector and expressed in E. coli BL21DE3. The maximum yield of recombinant proteins was optimized after 16 hrs of post induction at 21°C and purified the recombinant protein in soluble form. Antibodies were raised in Mice and Rabbit. The IgG antibody titer in the case of Mice was 1: 1,024,000 and Rabbit was 1: 512,000 with alum as adjuvant via intramascular route. The biological activity of the recombinant protein was confirmed by in-vitro studies using PC12 cells by the synaptobrevin cleavage, the rBoNT/B LC protein showed the maximum blockage of acetylcholine release at a concentration of 150nM rBoNT/B LC in comparison to the control cells. When the cells were incubated with rBoNT/B LC neutralized by the antisera raised against it, the acetylcholine release was equivalent to the control. IgG specific to rBoNT/B LC was purified from raised antibodies. The results showed that the developed antibody against rBoNT/B LC protein were able to detect botulinum toxin type B approximately up to 1 ng/ml. These developed high titer antibodies may prove useful for the detection of botulinum neurotoxins in food and clinical samples.

  17. Evaluation of quail and chicken embryos for the detection of botulinum toxin serotypes A, B, E and F activity.

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    Comparison of quail (Coturnix japonica) and chicken (Gallus domesticus) embryos for the detection of BoNT/A activity was conducted using equal dosages of toxin/g of embryo (quail at 7 g and chickens at 48 g). Quail embryos were injected at 0, 0.5 to 50 ng adn chicken embryos at 0, 3.4 to 342 ng and...

  18. Botulinum Toxin Injections: A Treatment for Muscle Spasms

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    ... Your Health Resources Drugs, Procedures & Devices Procedures & Devices Botulinum Toxin Injections: A Treatment for Muscle Spasms Botulinum Toxin Injections: A Treatment for Muscle Spasms Drugs, Procedures & ...

  19. Application of botulinum toxin in pain management.

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    Sim, Woo Seog

    2011-03-01

    Botulinum toxin has been used for the treatment of many clinical disorders by producing temporary skeletal muscle relaxation. In pain management, botulinum toxin has demonstrated an analgesic effect by reducing muscular hyperactivity, but recent studies suggest this neurotoxin could have direct analgesic mechanisms different from its neuromuscular actions. At the moment, botulinum toxin is widely investigated and used in many painful diseases such as myofascial syndrome, headaches, arthritis, and neuropathic pain. Further studies are needed to understand the exact analgesic mechanisms, efficacy and complications of botulinum toxin in chronic pain disorders.

  20. Application of Botulinum toxin Type A: An arsenal in dentistry

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    Lakshmana B Rao

    2011-01-01

    Full Text Available An extremely effective way of preventing damage to and enhancing treatment of dental hard tissues and restorations would be to ′′de-programme′′ the muscles responsible for excessive destructive forces and other gnathological-related diseases. The new paradigm is the intramuscular injection of Botulinum toxin type A (BOTOX into the affected muscles. It is a natural protein produced by anaerobic bacterium, Clostridium botulinum. The toxin inhibits the release of acetylcholine (ACH, a neurotransmitter responsible for the activation of muscle contraction and glandular secretion, and its administration results in reduction of tone in the injected muscle. There are seven distinct serotypes of Botulinum toxin, viz., A, B, C, D, E, F, and G, which differ in their potency, duration of action, and cellular target sites. This paper describes the different applications of BOTOX in dentistry.

  1. Botulinum toxins: mechanisms of action, antinociception and clinical applications.

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    Wheeler, Anthony; Smith, Howard S

    2013-04-05

    Botulinum toxin (BoNT) is a potent neurotoxin that is produced by the gram-positive, spore-forming, anaerobic bacterium, Clostridum botulinum. There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G. Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150kDa, which is cleaved by tissue proteinases into an active di-chain molecule: a heavy chain (H) of ∼100 kDa and a light chain (L) of ∼50 kDa held together by a single disulfide bond. Each serotype demonstrates its own varied mechanisms of action and duration of effect. The heavy chain of each BoNT serotype binds to its specific neuronal ecto-acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs. The light chain acts to cleave SNAP-25, which inhibits synaptic exocytosis, and therefore, disables neural transmission. The action of BoNT to block the release of acetylcholine botulinum toxin at the neuromuscular junction is best understood, however, most experts acknowledge that this effect alone appears inadequate to explain the entirety of the neurotoxin's apparent analgesic activity. Consequently, scientific and clinical evidence has emerged that suggests multiple antinociceptive mechanisms for botulinum toxins in a variety of painful disorders, including: chronic musculoskeletal, neurological, pelvic, perineal, osteoarticular, and some headache conditions.

  2. Botulinum toxin the poison that heals: A brief review.

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    Dutta, Shubha Ranjan; Passi, Deepak; Singh, Mahinder; Singh, Purnima; Sharma, Sarang; Sharma, Abhimanyu

    2016-01-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram-positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. This paper aims at discussing botulinum neurotoxin, its structure, mechanism of action, pharmacology, its serotypes and the reasons for wide use of type A, the various indications and contraindications of the use of botulinum neurotoxin and finally the precautions taken when botulinum neurotoxin is used as a treatment approach. We have searched relevant articles on this subject in various medical databases including Google Scholar, PubMed Central, ScienceDirect, Wiley Online Library, Scopus, and Copernicus. The search resulted in more than 2669 articles, out of which a total of 187 were reviewed. However, the review has been further constricted into only 54 articles as has been presented in this manuscript keeping in mind the page limitation and the limitation to the number of references. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin (BT) is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle-associated proteins responsible for acetylcholine release into the neuromuscular junction. A fascinating aspect of BT research in recent years has been the development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for the treatment of human diseases. The present review focuses on both warfare potential as well as medical uses of botulinum neurotoxin.

  3. Botulinum toxin — therapeutic effect in cosmetology

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    Morrison A.V.

    2016-09-01

    Full Text Available This review presents the data from published literatures and the research works conducted by the authors about mechanisms of action of botulinum toxin and its use in the practical medicine (particularly in dermatology and cosmetology. Indications and contraindications of botulinum toxin use in cosmetology are also considered in this work.

  4. From poison to remedy: the chequered history of botulinum toxin.

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    Erbguth, F J

    2008-01-01

    Botulinum toxin poisoning has afflicted mankind through the mists of time. However, the first incident of food-borne botulism was documented as late as the 18th century, when the consumption of meat and blood sausages gave rise to many deaths throughout the kingdom of Württemberg in South Western Germany. The district medical officer Justinus Kerner (1786--1862), who was also a well-known German poet, published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822 and attributed the intoxication to a biological poison. Kerner also postulated that the toxin might be used for treatment purposes. In 1895, an outbreak of botulism in the small Belgian village of Ellezelles led to the discovery of the pathogen "Clostridium botulinum" by Emile Pierre van Ermengem. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz in the early 1970s, when the type-A serotype was used in medicine to correct strabismus. Other preparations of the type-A toxin were developed and manufactured in the United Kingdom, Germany, and China, whereas a therapeutic type-B toxin was prepared in the United States. To date, the toxin has been used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain.

  5. Evaluation of a quail embryo model for the detection of botulinum toxin type A activity

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    The quail embryo was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving 20 ng of BoNT or higher had m...

  6. Botulinum A toxin utilizations in obstetric palsy

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    Atakan Aydin

    2012-12-01

    Conclusion: We conclude that with the help of botulinum A toxin and physyotherapy, obstetrical palsy patient with cocontractions can significantly improve movements and may have less surgery. [Hand Microsurg 2012; 1(3.000: 89-94

  7. [Botulinum toxin as a biological weapon].

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    Rossow, Heidi; Kinnunen, Paula M; Nikkari, Simo

    2012-01-01

    Botulism is caused by botulinum neurotoxin produced by the bacterium Clostridium botulinum. It is a flaccid paralysis in which consciousness and nociception are preserved. Natural botulism typically results from ingestion of inadequately heated or unheated vacuum-packed foods. In addition, botulinum toxin is one of the most feared biological weapons. In the diagnosis and treatment of botulism early suspicion is essential. Several coinciding or local clusters without a typical connecting source, or an uncommon type of toxin may indicate an intentionally caused epidemic.

  8. Botulinum toxin in ophthalmic plastic surgery

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    Naik Milind

    2005-01-01

    Full Text Available Botulinum toxin chemodenervation has evolved greatly over the past 30 years since its introduction in the 1970s for the management of strabismus. Among ophthalmic plastic surgeons, botulinum toxins are often used as the first line treatment for facial dystonias. These toxins are also efficacious for the temporary management of various other conditions including keratopathies (through so called chemo-tarsorraphy, upper eyelid retraction, orbicularis overaction-induced lower eyelid entropion, gustatory epiphora, Frey′s syndrome, and dynamic facial rhytids such as lateral canthal wrinkles (crow′s feet, glabellar creases and horizontal forehead lines. This article describes the pharmacology, reconstitution techniques and common current applications of botulinum toxins in ophthalmic plastic surgery.

  9. Botulinum toxin and its clinical aspects: An overview

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    Shatavisa Mukherjee

    2015-01-01

    Full Text Available Botulinum toxin (BTX, a potent neurotoxin which is produced by the bacterium Clostridium botulinum, consists of eight distinct neurotoxin serotypes referred to as (BTX type-A [BTX-A], B, C, D, E, F, G, H all of which inhibit acetylcholine release at the neuromuscular junction. BTX-A, by blocking acetylcholine release at neuromuscular junctions, accounts for its therapeutic action to relieve dystonia, spasticity, and related disorders. A wide variety of medical conditions such as bruxism, hyperhidrosis, achalasia, focal dystonia, upper motor neuron syndrome, blepharospasm, and chronic migraine are now treated with BTX. The cosmetological applications include correction of lines, creases, and wrinkling all over the face, chin, neck, and chest. Side effects are generally rare and minimal. Injections with BTX-A are well-tolerated. Discovery of further newer indications of this neurotoxin can enlighten the path of research in the field of neuroscience.

  10. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.

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    Patil, Shilpadevi; Willett, Olga; Thompkins, Terin; Hermann, Robert; Ramanathan, Sathish; Cornett, Elyse M; Fox, Charles J; Kaye, Alan David

    2016-03-01

    Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients.

  11. Treatment of Frontal Hyperhidrosis With Botulinum Toxin

    Directory of Open Access Journals (Sweden)

    Ayşe Esra Koku Aksu

    Full Text Available Focal hyperhidrosis is usually localized to the axillae, palms and soles. Less frequently, hyperhidrosis may be confined to the forehead and may have negative impact on patient’s quality of life. A 34-year-old man presented to our clinic with the complaint of frontal hyperhidrosis. He was treated with botulinum toxin A. Thirty points were marked over the forehead and at each injection point, 0.15 ml (3U botulinum toxin A were injected intracutaneously. Hyperhidrosis was significantly reduced and the effect lasted for 12 months. Skindex-29, a quality-of-life measure for skin disease, was administered to the patient at the beginning and at the end of second week of botulinum toxin A injection. There was a significant improvement on the Skindex-29 scale at the end of the treatment. There was no any side effect detected during and after the treatment. Botulinum toxin A treatment is considered to be effective and safe for frontal hyperhidrosis.

  12. Noncosmetic periocular therapeutic applications of botulinum toxin

    Directory of Open Access Journals (Sweden)

    Kaynak-Hekimhan Pelin

    2010-01-01

    Full Text Available Botulinum toxin blocks acetylcholine release at the neuromuscular junction. The drug which was initially found to be useful in the treatment of strabismus has been extremely effective in the treatment of variety of conditions, both cosmetic and noncosmetic. Some of the noncosmetic uses of botulinum toxin applications include treatment of spastic facial dystonias, temporary treatment of idiopathic or thyroid dysfunction-induced upper eyelid retraction, suppression of undesired hyperlacrimation, induction of temporary ptosis by chemodenervation in facial paralysis, and correction of lower eyelid spastic entropion. Additional periocular uses include control of synchronic eyelid and extraocular muscle movements after aberrant regeneration of cranial nerve palsies. Cosmetic effects of botulinum toxin were discovered accidentally during treatments of facial dystonias. Some of the emerging nonperiocular application for the drug includes treatment of hyperhidrosis, migraine, tension-type headaches, and paralytic spasticity. Some of the undesired side effects of periocular applications of botulinum toxin inlcude ecchymosis, rash, hematoma, headache, flu-like symptoms, nausea, dizziness, loss of facial expression, lower eyelid laxity, dermatochalasis, ectropion, epiphora, eyebrow and eyelid ptosis, lagophthalmos, keratitis sicca, and diplopia.

  13. Purification and characterization of neurotoxin complex from a dual toxin gene containing Clostridium Botulinum Strain PS-5.

    Science.gov (United States)

    Singh, Ajay K; Sachdeva, Amita; Degrasse, Jeffrey A; Croley, Timothy R; Stanker, Larry H; Hodge, David; Sharma, Shashi K

    2013-04-01

    Botulinum neurotoxins are produced as a toxin complex (TC) which consists of neurotoxin (NT) and neurotoxin associated proteins. The characterization of NT in its native state is an essential step for developing diagnostics and therapeutic countermeasures against botulism. The presence of NT genes was validated by PCR amplification of toxin specific fragments from genomic DNA of Clostridium botulinum strain PS-5 which indicated the presence of both serotype A and B genes on PS-5 genome. Further, TC was purified and characterized by Western blotting, Digoxin-enzyme linked immunosorbent assay, endopeptidase activity assay, and Liquid chromatography-Mass spectrometry. The data showed the presence of serotype A specific neurotoxin. Based on the analysis of neurotoxin genes and characterization of TC, PS-5 strain appears as a serotype A (B) strain of C. botulinum which produces only serotype A specific TC in the cell culture medium.

  14. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

    Directory of Open Access Journals (Sweden)

    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  15. Beneficial effects of botulinum toxin type A in trigeminal neuralgia

    OpenAIRE

    Zúñiga, Carlos; Díaz,Sergio; Piedimonte, Fabián; Micheli, Federico

    2008-01-01

    Botulinum toxin has been thoroughly studied as a potential tool in the treatment of several pain syndromes. Therefore, we assessed the clinical effects of botulinum toxin type A injections in 12 patients with otherwise unresponsive idiopathic trigeminal neuralgia. Patients were infiltrated with 20-50 units of botulinum toxin in trigger zones. Those who presented with mandibular involvement were also infiltrated in the masseter muscle. The patients were assessed on a weekly basis using the Vis...

  16. Beneficial effects of botulinum toxin type A in trigeminal neuralgia

    OpenAIRE

    Carlos Zúñiga; Sergio Díaz; Fabián Piedimonte; Federico Micheli

    2008-01-01

    Botulinum toxin has been thoroughly studied as a potential tool in the treatment of several pain syndromes. Therefore, we assessed the clinical effects of botulinum toxin type A injections in 12 patients with otherwise unresponsive idiopathic trigeminal neuralgia. Patients were infiltrated with 20-50 units of botulinum toxin in trigger zones. Those who presented with mandibular involvement were also infiltrated in the masseter muscle. The patients were assessed on a weekly basis using the Vis...

  17. Human Monoclonal Antibodies as a Countermeasure Against Botulinum Toxins

    Science.gov (United States)

    2012-11-30

    REPORT Human monoclonal antibodies as a countermeasure against Botulinum toxins 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: In this report, we...Prescribed by ANSI Std. Z39.18 - 31-Aug-2012 Human monoclonal antibodies as a countermeasure against Botulinum toxins Report Title ABSTRACT In this report...DTRA Final Report: Human monoclonal antibodies as a countermeasure against Botulinum toxins   Page 1 of 22 DTRA Final Report: Human monoclonal

  18. The Mechanism of the Beneficial Effect of Botulinum Toxin Type a Used in the Treatment of Temporomandibular Joints Dysfunction.

    Science.gov (United States)

    Malgorzata, Pihut; Piotr, Ceranowicz; Edward, Kijak

    2017-01-01

    In the course of temporomandibular joint, dysfunctions very often occur to the excessive increase in tension of masticatory muscles, so the main aim of the treatment is reduction of this hypertension of muscles. For this reason, we use botulinum toxin type A, which is produced by Grampositive Clostridium bacteria. There are six serotypes of the toxin: A, B, C, D, E, F, and G. The botulinum toxin type A was first isolated in 1920s. Today, botulinum toxin type A is used increasingly more often as an efficient and patient-friendly therapy in neurology, ophthalmology, neurology, urology and laryngology. The aim of the article was to review the literature and description of the current knowledge concerned with mechanism of action of botulinum toxin type A, clinical applications and metabolic determinants of muscle contraction and the beneficial effect of this drug on the state of muscle tension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Botulinum toxin therapy for abductor spasmodic dysphonia.

    Science.gov (United States)

    Woodson, Gayle; Hochstetler, Heidi; Murry, Thomas

    2006-03-01

    Botulinum toxin has been widely accepted as an effective therapy for controlling the symptoms of adductor spasmodic dysphonia (ADSD). Reported experience with botulinum treatment for abductor spasmodic dysphonia (ABSD) has been less impressive. Factors that may impair outcomes for ABSD include differences in the pathophysiology of ADSD and ABSD and limitation of maximal dose from airway restriction with posterior cricoarytenoid muscle (PCA) weakness. We report our experience with botulinum injection of the PCA with an asymmetric dose escalation protocol, based on clinical observations that in ABSD, abductor spasms are often stronger on one side, usually the left. The nondominant side was injected with 1.25 units. Dominant side dose began at 5 units, with step-wise increments of 5 units per week until one of three endpoints was reached: Elimination of breathy voice breaks, complete abductor paralysis of the dominant side, or airway compromise. Fourteen of 17 patients achieved good or fair voice, with dominant-side doses ranging from 10 to 25 units. Exercise intolerance limited PCA dose in two patients. One patient had persisting breathiness that improved with medialization thyroplasty. Asymmetric botulinum toxin injection into PCA muscles can suppress abductor spasm in patients with ABSD, but breathiness may persist, because of inadequate glottal closure.

  20. USE OF BOTULINUM TOXIN TYPE A IN THE TREATMENT OF SPASTICITY IN CHILDREN WITH CEREBRAL PALSY

    Directory of Open Access Journals (Sweden)

    Ljiljana Lazić

    2011-06-01

    Full Text Available Cerebral palsy has an incidence of about 1-2 per 1000 live births, and in spite of the progress of neonatal medicine, it seems that the incidence will not subside in the near future. The most important characteristic of cerebral palsy is movement abnormality: spasticity, chorea, athetosis, ataxia, dystonia, as well as their different combinations. About 70% of children who suffer from cerebral palsy also suffer from some form of spasticity. Spasticity is a type of muscle hypertonicity characterized by rapid increase in resistance to passive stretching of muscles. The interest for botulinum toxin application in the treatment of spasticity has dramatically increased in the last 10 years. Botulinum toxin is the most powerful neurotoxin that is found in nature. It is produced by anaerobic bacteria – clostridium botulinum. It is produced in eight serotypes of which type A is the most commonly used. Botulinum toxin blocks neuromuscular transmission and causes irreversible weakness of the treated muscle. It has been used since 1993 in the treatment of cerebral palsy in children. The toxin effect is permanent and it results in irreversible denervation. Functional recovery is possible after 2-4 months, due to sprouting of nerve endings and the formation of new synaptic contacts. Treatment with botulinum toxin is safe. Adverse effects are rare, temporary and completely reversible. Application of botulinum toxin prevents or reduces contractures and deformities, and thus delays or avoids surgical treatment. Yet, physical therapy, which prolongs and improves the effects of botulinum toxin, remains an essential and most important form of therapy in the treatment of children with cerebral palsy.

  1. Botulinum Toxin in the Treatment of Facial Paralysis.

    Science.gov (United States)

    Mehdizadeh, Omid B; Diels, Jacqueline; White, William Matthew

    2016-02-01

    This article reviews the current literature supporting the use of botulinum toxin in producing symmetric facial features and reducing unwanted, involuntary movements. Methods, protocols, and adverse events are discussed. Additionally, the authors suggest that using botulinum toxin A therapy in postparalytic facial synkinesis can provide long-term results when used in conjunction with other treatment modalities.

  2. Botulinum toxin for meralgia paresthetica in type 2 diabetes.

    Science.gov (United States)

    Dhull, Pawan; Tewari, A K; Upreti, Vimal; Prakash, M S; Hari Kumar, K V S

    2013-01-01

    Botulinum toxin has been used for a variety of neuropathic conditions in diabetes mellitus. Meralgia paresthetica is a mononeuropathy of femoral nerve seen in diabetes and obesity with an unclear etiopathogenesis. We studied the role of botulinum toxin in resistant cases of meralgia paresthetica in type 2 diabetes. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

    Science.gov (United States)

    Mor, Niv; Tang, Christopher; Blitzer, Andrew

    2016-09-01

    Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD.

  4. Botulinum toxins: Pharmacology and its current therapeutic evidence for use

    Directory of Open Access Journals (Sweden)

    Muthane U

    2003-10-01

    Full Text Available Botulinum toxins are, as a group, among the most potent neuromuscular toxins known, yet they are clinically useful in the management of conditions associated with muscular and glandular over-activity. Botulinum toxins act by preventing release of acetylcholine into the neuromuscular junction. While botulinum toxin type A is commonly available, different manufacturers produce specific products, which are not directly interchangeable and should not be considered as generically equivalent formulations. Type B is also available in the market. Each formulation of botulinum toxin is unique with distinct dosing, efficacy and safety profiles for each use to which it is applied. Botulinum toxin type A is the treatment of choice based on its depth of evidence in dystonias and most other conditions. Botulinum toxin type A is established as useful in the management of spasticity, tremors, headache prophylaxis and several other neurological conditions. Active research is underway to determine the parameters for which the type B toxin can be used in these conditions, as covered in this review. Botulinum toxin use has spread to several fields of medicine.

  5. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    Science.gov (United States)

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

  6. Botulinum toxin for treatment of glandular hypersecretory disorders.

    LENUS (Irish Health Repository)

    Laing, T A

    2012-02-03

    SUMMARY: The use of botulinum toxin to treat disorders of the salivary glands is increasing in popularity in recent years. Recent reports of the use of botulinum toxin in glandular hypersecretion suggest overall favourable results with minimal side-effects. However, few randomised clinical trials means that data are limited with respect to candidate suitability, treatment dosages, frequency and duration of treatment. We report a selection of such cases from our own department managed with botulinum toxin and review the current data on use of the toxin to treat salivary gland disorders such as Frey\\'s syndrome, excessive salivation (sialorrhoea), focal and general hyperhidrosis, excessive lacrimation and chronic rhinitis.

  7. Botulinum toxin in the treatment of sialorrhea

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    Svetel Marina

    2009-01-01

    Full Text Available Background/Aim. Botulinum toxin-A (BTX-A is known to block the release of acetylcholine from motor and autonomic nerve terminals and may significantly decrease saliva production when injected intraglandulary. The aim of this study was to evaluate effects of BTX-A injections in the treatment of disabling sialorrhea in various neurological disorders. Methods. This study included 19 consecutive patients with significant sialorrhea associated with various neurological disorders. Out of them 13 patients were with Parkinson's disease, two with pantothenate kinase-associated neurodegeneration, two with multiple system atrophy, one with Wilson's disease, and one patient with postoperative sialorrhea. Botulinum toxin-A (Dysport®, Ipsen Pharma was injected into the parotid glands with (n = 7 patients or without (n = 12 patients ultrasound guidance. All the patients were scored before and after the treatment and in weekly intervals thereafter using the salivation item of the part II (Activities of Daily Living of the Unified Parkinson's Disease Rating Scale (UPDRS. Results. Thirteen patients (68% reported beneficial effect of BTX-A injection, while 6 of them (32% had no response at all. The sialorrhea scores before and after the treatment were 3.1 ± 0.1 (range 2-4 and 1.8 ± 0.1 (range 0- 3, respectively (t = 5.636; p < 0.001. There was no difference in the magnitude of response between the groups with (t = 4.500; p = 0.004 and without (t = 3.674; p = 0.005 ultrasound control of injection sites. Adverse effects were registered in 5 patients (26%. Conclusions. Botulinum toxin-A injections to easily accessible parotid glands, without necessity for ultrasound guidance, are safe and efficaceous treatment for sialorrhea in different neurological disorders.

  8. Botulinum toxin in the treatment of sialorrhea.

    Science.gov (United States)

    Svetel, Marina; Vasić, Milan; Dragasević, Natasa; Pekmezović, Tatjana; Petrović, Igor; Kostić, Vladimir

    2009-01-01

    Botulinum toxin-A (BTX-A) is known to block the release of acetylcholine from motor and autonomic nerve terminals and may significantly decrease saliva production when injected intraglandulary. The aim of this study was to evaluate effects of BTX-A injections in the treatment of disabling sialorrhea in various neurological disorders. This study included 19 consecutive patients with significant sialorrhea associated with various neurological disorders. Out of them 13 patients were with Parkinson's disease, two with pantothenate kinase-associated neurodegeneration, two with multiple system atrophy, one with Wilson's disease, and one patient with postoperative sialorrhea. Botulinum toxin-A (Dysport, Ipsen Pharma) was injected into the parotid glands with (n=7 patients) or without (n=12 patients) ultrasound guidance. All the patients were scored before and after the treatment and in weekly intervals thereafter using the salivation item of the part II (Activities of Daily Living) of the Unified Parkinson's Disease Rating Scale (UPDRS). Thirteen patients (68%) reported beneficial effect of BTX-A injection, while 6 of them (32%) had no response at all The sialorrhea scores before and after the treatment were 3.1 +/- 0.1 (range 2-4) and 1.8 +/- 0.1 (range 0-3), respectively (t=5.636; p<0.001). There was no difference in the magnitude of response between the groups with (t=4.500; p=0.004) and without (t=3.674; p=0.005) ultrasound control of injection sites. Adverse effects were registered in 5 patients (26%). Botulinum toxin-A injections to easily accessible parotid glands, without necessity for ultrasound guidance, are safe and efficaceous treatment for sialorrhea in different neurological disorders.

  9. Botulinum toxin for treatment of restrictive strabismus.

    Science.gov (United States)

    Merino, Pilar S; Vera, Rebeca E; Mariñas, Laura G; Gómez de Liaño, Pilar S; Escribano, Jose V

    To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  10. Ultrasound-guided botulinum toxin injections

    Directory of Open Access Journals (Sweden)

    S. E. Khatkova

    2016-01-01

    Full Text Available One of the key conditions for achieving the desirable result during botulinum toxin therapy for muscular dystonia, spasticity, and other diseases accompanied by spasm, pain, and autonomic dysfunction (dystonias, spasticity, etc. is the proper administration of the agent into the muscles directly involved in the pathological process. The exact entry of botulinum toxin into the target muscles is essential for successful and safe treatment because its injection into a normal muscle may cause side effects. The most common errors are the incorrect depth and incorrect direction of a needle on insertion. Therefore, the exact injection of the agent particularly into the shallow and deep muscles is a difficult task even for an experienced specialist and requires the use of controlling methods.The European Consensus on Botulinum Toxin Therapy points out that various injection techniques are needed for the better identification of necessary muscles. However, there are currently no reports on the clear advantage of any technique. In our country, injections using palpation and anatomical landmarks have been widely used in routine practice so far; electromyographic monitoring and electrostimulation have been less frequently applied. In recent years, the new method ultrasound-guided injection has continued to grow more popular. This effective, accessible, and easy-to-use method makes it possible to manage a real-time injection process and to ensure the exact entry of the agent into the muscle. This paper is dedicated to a comparative analysis of different injection methods and to a description of the ultrasound-guided technique and its advantages over others. 

  11. Effects of Transgenic Expression of Botulinum Toxins in Drosophila

    OpenAIRE

    Backhaus, Philipp

    2017-01-01

    Clostridial neurotoxins (botulinum toxins and tetanus toxin) disrupt neurotransmitter release by cleaving neuronal SNARE proteins. We generated transgenic flies allowing for conditional expression of different botulinum toxins and evaluated their potential as tools for the analysis of synaptic and neuronal network function in Drosophila melanogaster by applying biochemical assays and behavioral analysis. On the biochemical level, cleavage assays in cultured Drosophila S2 cells were performed ...

  12. Acrylamide inhibits nerve sprouting induced by botulinum toxin type A

    Institute of Scientific and Technical Information of China (English)

    Hong Jiang; Yi Xiang; Xingyue Hu; Huaying Cai

    2014-01-01

    Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3-4 months, muscle strength usually recovers because function-al recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce neurotoxic substances that cause retrograde necrotizing neuropathy and inhibit nerve sprouting caused by botulinum toxin type A. This study investigated whether acrylamide inhibits nerve sprouting after intramuscular injection of botulinum toxin type A. A tibial nerve sprouting model was established through local injection of botulinum toxin type A into the right gastrocnemius muscle of Sprague-Dawley rats. Following intramuscular injection, rats were given intraperitoneal injection of 3%acrylamide every 3 days for 21 days. Nerve sprout-ing appeared 2 weeks after intramuscular injection of botulinum toxin type A and single-fiber electromyography revealed abnormal conduction at the neuromuscular junction 1 week after intra-muscular injection of botulinum toxin type A. Following intraperitoneal injection of acrylamide, the peak muscle ifber density decreased. Electromyography jitter value were restored to normal levels 6 weeks after injection. This indicates that the maximal decrease in ifber density and the time at which functional conduction of neuromuscular junction was restored were delayed. Addition-ally, the increase in tibial nerve ifbers was reduced. Acrylamide inhibits nerve sprouting caused by botulinum toxin type A and may be used to prolong the clinical dosage of botulinum toxin type A.

  13. Botulinum toxin physiology in focal hand and cranial dystonia.

    Science.gov (United States)

    Karp, Barbara Illowsky

    2012-11-20

    The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders.

  14. Botulinum Toxin Physiology in Focal Hand and Cranial Dystonia

    Directory of Open Access Journals (Sweden)

    Barbara Illowsky Karp

    2012-11-01

    Full Text Available The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders.

  15. Cosmetic Effect of Botulinum Toxin In Focal Hyperhydrosis

    Directory of Open Access Journals (Sweden)

    Jain S

    2005-01-01

    Full Text Available Hyperhydrosis of axillae, palm and sole is not a very uncommon problem. It leads to great embarrassment and considerable emotional stress to the individuals. Botulinum toxins prevent the release of acetylcholine at nerve terminals, therefore, reduces sweat secretion. Six patients of axillary and 4 patients of palmer and planter hyperhydrosis were treated with botulinum toxin. All patients experienced relatively satisfactory reduction of hyperhydrosis for period ranging between 4-7 months. No adverse effects were observed. Botulinum toxin therefore can be considered as an effective treatment in focal hyperhydrosis.

  16. The history of Botulinum toxin: from poison to beauty.

    Science.gov (United States)

    França, Katlein; Kumar, Anagha; Fioranelli, Massimo; Lotti, Torello; Tirant, Michael; Roccia, Maria Grazia

    2017-03-15

    Botulinum toxin, also called the "miracle toxin," is a neurotoxin produced by the bacteria Clostridium botulinum. It is known to block nerve signals that contract muscles resulting in a temporary paralysis of the muscles. Toxins type A and B have been extensively studied and utilized in the realm of beauty and cosmetology. Initially, the toxin gained popularity as a disease-causing "poison". It was only later that it found its way to becoming a must have in modern aesthetic practice. Today, this wonder toxin has proven to be an apt and convenient option in the field of anti-aging medicine.

  17. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke

    Science.gov (United States)

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-01-01

    Abstract Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases. This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance. During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization. The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia. PMID:26266368

  18. Experience with botulinum toxin in the treatment of cerebral palsy

    African Journals Online (AJOL)

    To asseS5 the effect of botulinum toxin on dynamic spasticity and dystonic posturing in children "Yith cerebral palsy. Design. ... muscles responsible for abnormal posture and movement. Institute of Child .... SUbsequently the right foot was fully ...

  19. CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.

    Energy Technology Data Exchange (ETDEWEB)

    SWAMINATHAN,S.; ESWARAMOORTHY,S.

    2001-11-19

    The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].

  20. Botulinum toxin drugs: brief history and outlook.

    Science.gov (United States)

    Dressler, D

    2016-03-01

    The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur.

  1. Botulinum Toxin to Treat Neurogenic Bladder.

    Science.gov (United States)

    Smith, Christopher P; Chancellor, Michael B

    2016-02-01

    Alteration in neural control from suprapontine areas to the nerves innervating the bladder can lead to bladder dysfunction and the development of a neurogenic bladder (NGB). Patients with NGB often suffer from urinary incontinence, which can lead to adverse events such as urinary tract infections and decubiti, in addition to creating a large care burden for family members or healthcare providers and significantly impairing patient quality of life. The common failure of anticholinergic medications has spurned the development of second-line treatments, including the use of botulinum toxin. OnabotulinumtoxinA (onaBoNT-A; BOTOX, Allergan, Inc.) was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat neurogenic detrusor overactivity in patients with urinary incontinence resulting from a NGB. In this review the authors summarize pertinent results from key trials leading to FDA approval of onaBoNT-A as well as more recent long-term data.

  2. Botulinum toxin A for the Treatment of Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Po-Fan Hsieh

    2016-02-01

    Full Text Available The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA and European Association of Urology (EAU guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

  3. Botulinum toxin A for the Treatment of Overactive Bladder.

    Science.gov (United States)

    Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

    2016-02-29

    The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

  4. A mixed treatment comparison to compare the efficacy and safety of botulinum toxin treatments for cervical dystonia.

    Science.gov (United States)

    Han, Yi; Stevens, Andrea L; Dashtipour, Khashayar; Hauser, Robert A; Mari, Zoltan

    2016-04-01

    A systematic pair-wise comparison of all available botulinum toxin serotype A and B treatments for cervical dystonia (CD) was conducted, as direct head-to-head clinical trial comparisons are lacking. Five botulinum toxin products: Dysport(®) (abobotulinumtoxinA), Botox(®) (onabotulinumtoxinA), Xeomin(®) (incobotulinumtoxinA), Prosigne(®) (Chinese botulinum toxin serotype A) and Myobloc(®) (rimabotulinumtoxinB) have demonstrated efficacy for managing CD. A pair-wise efficacy and safety comparison was performed for all toxins based on literature-reported clinical outcomes. Multi-armed randomized controlled trials (RCTs) were identified for inclusion using a systematic literature review, and assessed for comparability based on patient population and efficacy outcome measures. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was selected as the efficacy outcome measurement for assessment. A mixed treatment comparison (MTC) was conducted using a Bayesian hierarchical model allowing indirect comparison of the interventions. Due to the limitation of available clinical data, this study only investigated the main effect of toxin treatments without explicitly considering potential confounding factors such as gender and formulation differences. There was reasonable agreement between the number of unconstrained data points, residual deviance and pair-wise results. This research suggests that all botulinum toxin serotype A and serotype B treatments were effective compared to placebo in treating CD, with the exception of Prosigne. Based on this MTC analysis, there is no significant efficacy difference between Dysport, Botox, Xeomin and Myobloc at week four post injection. Of the adverse events measured, neither dysphagia nor injection site pain was significantly greater in the treatment or placebo groups.

  5. An aptamer beacon responsive to botulinum toxins.

    Science.gov (United States)

    Bruno, John G; Richarte, Alicia M; Carrillo, Maria P; Edge, Allison

    2012-01-15

    Sixty candidate DNA aptamers were developed against botulinum neurotoxin (BoNT) type A light chain (LC) from ten rounds of selection, resulting in several identical sequences. Secondary structures of the identical aptamers were compared to structures of previously reported BoNT A DNA aptamers. A series of ten candidate loop structures were selected from this comparison as potential binding pockets and aptamer beacons. These candidate beacons were synthesized with 5'-TYE 665 and 3'-Iowa Black quencher labels for comparison of fluorescence levels as a function of BoNT A LC concentration. Only three of the ten candidates exhibited any fluorescence response to increasing levels of BoNT A LC. However, of the two most responsive candidates, one represented a subset loop of the larger more intensely fluorescent double-looped structure, designated Beacon 10. This beacon yielded a lower limit of detection of 1 ng/mL in buffer using a spectrofluorometer and a portable handheld fluorometer, but also responded substantially to BoNT A, B, E holotoxins and heavy or light chain components even in a dilute soil suspension, but not in 50% human serum. Beacon 10 did not respond strongly to a variety of other divergent peptides, suggesting that it is relatively specific to the level of botulinum toxins and is only useful for environmental testing. Beacon 10 also shared short sequence segments with other published BoNT aptamer DNA sequences, suggesting that these may be points of physical contact between the aptamers and BoNTs.

  6. Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A

    Directory of Open Access Journals (Sweden)

    Tina I. Lam

    2016-12-01

    Full Text Available Botulinum neurotoxins (BoNTs are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that both BoNT serotype A complex and holotoxin can bind and transit through the intestinal epithelia to disseminate in the blood. The timing of BoNT/A toxin internalization was shown to be comparable in both the Caco-2 in vitro cell culture and in the oral mouse intoxication models. Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins. In this study, we evaluate whether probiotic microorganisms will block BoNT/A uptake in the in vitro cell culture system using Caco-2 cells. Several probiotics tested (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri blocked BoNT/A uptake in a dose-dependent manner whereas a non-probiotic strain of Escherichia coli did not. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor by sequestration of toxin via binding to probiotics. These results show for the first time that probiotic treatment can inhibit BoNT/A binding and internalization in vitro and may lead to the development of new therapies.

  7. Development of a quail embryo model for the detection of botulinum toxin type A activity

    Science.gov (United States)

    Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

  8. Treatment of Palatal Myoclonus with Botulinum Toxin Injection

    Directory of Open Access Journals (Sweden)

    Mursalin M. Anis

    2013-01-01

    Full Text Available Palatal myoclonus is a rare cause of pulsatile tinnitus in patients presenting to the otolaryngology office. Rhythmic involuntary contractions of the palatal muscles produce the pulsatile tinnitus in these patients. Treatment of this benign but distressing condition with anxiolytics, anticonvulsants, and surgery has been largely unsuccessful. A few investigators have obtained promising results with botulinum toxin injection into the palatal muscles. We present a patient with palatal myoclonus who failed conservative treatment with anxiolytics. Unilateral injection of botulinum toxin into her tensor veli palatini muscle under electromyographic guidance resolved pulsatile tinnitus in her ipsilateral ear and unmasked pulsatile tinnitus in the contralateral ear. A novel method of following transient postinjection symptoms using a diary is presented in this study. Botulinum toxin dose must be titrated to achieve optimal results in each individual patient, analogous to titrations done for spasmodic dysphonia. Knowledge of the temporal onset of postinjection side effects and symptomatic relief may aid physicians in dose titration and surveillance. We present suggestions on titrating the botulinum toxin dose to optimal levels. A review of the literature on the use of botulinum toxin for palatal myoclonus and some common complications are discussed.

  9. Botulinum toxin A, brain and pain.

    Science.gov (United States)

    Matak, Ivica; Lacković, Zdravko

    2014-01-01

    Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now.

  10. Why do females use botulinum toxin injections?

    Directory of Open Access Journals (Sweden)

    Carter Singh

    2015-01-01

    Full Text Available Background: Botulinum toxin (BT use for enhancing the facial features has become a commonly accepted form of aesthetic intervention. This study conducted a self-report survey of female BT users in order to explore the motivating factors in its use (cost-benefit analysis. Settings and Design: This is a cross-sectional exploratory pilot study. Materials and Methods: Self-report questionnaires were administered to 41 consecutive clients attending an independent medical practice for BT injections for cosmetic purposes. All the participants were females and represented a range of age groups from the 20s to above 60s. Items in the nonstandardized questionnaire elicited questions relating to the reasons for and against BT use. Statistical Analysis Used: Descriptive analysis was used rather than inferential statistics, and involved ranking the responses according to the most likely reasons for using BT and disadvantages of its use. Results: In general, the primary motivating factor for BT use was to improve self-esteem, and the greatest disadvantage involved financial costs associated with the procedure. Conclusions: The main findings of this study suggest that females who use BT for aesthetic purposes are motivated by personal psychological gains (intrapersonal attributes rather than social gains (interpersonal factors. In other words, they do not believe that having BT will equate to being treated any better by other people but would rather provide them with confidence and satisfaction regarding their self-image.

  11. Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management.

    Science.gov (United States)

    Lan Chun, Chan; Kahn, Chase I; Borchert, Andrew J; Byappanahalli, Muruleedhara N; Whitman, Richard L; Peller, Julie; Pier, Christina; Lin, Guangyun; Johnson, Eric A; Sadowsky, Michael J

    2015-04-01

    The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophora spp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011-2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed in Cladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 10(0)-10(4) MPN/g dried algae, which was much greater (up to 10(3) fold) than that found in sand or the water column, indicating that Cladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putative C. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

  12. Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management

    Science.gov (United States)

    Chun, Chan Lan; Kahn, Chase I.; Borchert, Andrew J.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Peller, Julie R.; Pier, Christina; Lin, Guangyun; Johnson, Eric A.; Sadowsky, Michael J.

    2015-01-01

    The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophoraspp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011–2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed inCladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 100–104 MPN/g dried algae, which was much greater (up to 103 fold) than that found in sand or the water column, indicating thatCladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putativeC. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

  13. Ten Mistakes To Avoid When Injecting Botulinum Toxin.

    Science.gov (United States)

    Ruiz-Rodriguez, R; Martin-Gorgojo, A

    2015-01-01

    Injection of botulinum toxin is currently the most common cosmetic procedure in the United States, and in recent years it has become-together with dermal fillers-the mainstay of therapy for the prevention and treatment of facial aging. However, in some cases the treatment may lead to a somewhat unnatural appearance, usually caused by loss of facial expression or other telltale signs. In the present article, we review the 10 mistakes that should be avoided when injecting botulinum toxin. We also reflect on how treatment with botulinum toxin influences us through our facial expressions, both in terms of how we feel and what others perceive. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  14. Botulinum toxin improves reduced dorsiflexion after Achilles tendon surgery.

    Science.gov (United States)

    Reuter, Iris; Lorbach, Olaf; Mehnert, Sabine; Kaps, Manfred; Engelhardt, Martin

    2010-02-01

    Generally, outcome after surgical repair of complete Achilles tendon rupture is good. However, some patients have ongoing problems with dorsiflexion of the ankle joint. We report on eight patients, who did not achieve heel contact because of reduced ankle dorsiflexion 5 months after surgical repair of complete Achilles tendon rupture. All patients received at least three cycles of injections with 200-300 units of Botulinum toxin A (BOTOX) into the gastrocnemius and soleus muscle. Weakening of the triceps surae by Botulinum toxin allowed patients to perform the required exercises and to tolerate casting at night. Thus, all patients were able to tolerate plantigrade foot position 9 months after beginning of Botulinum toxin treatment. At final follow-up after 2 years, pain had significantly improved, and a mean dorsiflexion of 21 degrees was reached. In conclusion, treatment of the calf muscles with BOTOX is a safe and effective method to improve restricted dorsiflexion in patients after Achilles tendon repair.

  15. Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia

    Directory of Open Access Journals (Sweden)

    Kuan-Hsiang Lin

    2013-05-01

    Full Text Available Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required.

  16. Treatment of displaced mandibular condylar fracture with botulinum toxin A.

    Science.gov (United States)

    Akbay, Ercan; Cevik, Cengiz; Damlar, Ibrahim; Altan, Ahmet

    2014-04-01

    The aim of this case report is to discuss the effect on condylar reduction of botulinum toxin A treatment used in a child with displaced fracture at condylar neck of mandible. A 3-years old boy was admitted to our clinic for incomplete fracture of mandibular symphysis and displaced condylar fracture at the left side. An asymmetrical occlusal splint with intermaxillary fixation was used instead of open reduction and internal fixation because of incomplete fracture of symphysis and possible complications of condyle surgery. However, it was observed that condylar angulation persisted despite this procedure. Thus, botulinum toxin A was administered to masseter, temporalis and pterygoideus medialis muscles. At the end of first month, it was seen that mandibular condyle was almost completely recovered and that fusion was achieved. In conclusion, Botulinum A toxin injection aiming the suppression of masticatory muscle strength facilitates the reduction in the conservative management of displaced condyle in pediatric patients.

  17. Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani.

    Science.gov (United States)

    Connan, Chloé; Denève, Cécile; Mazuet, Christelle; Popoff, Michel R

    2013-12-01

    Botulinum and tetanus neurotoxins are structurally and functionally related proteins that are potent inhibitors of neuroexocytosis. Botulinum neurotoxin (BoNT) associates with non-toxic proteins (ANTPs) to form complexes of various sizes, whereas tetanus toxin (TeNT) does not form any complex. The BoNT and ANTP genes are clustered in a DNA segment called the botulinum locus, which has different genomic localization (chromosome, plasmid, phage) in the various Clostridium botulinum types and subtypes. The botulinum locus genes are organized in two polycistronic operons (ntnh-bont and ha/orfX operons) transcribed in opposite orientations. A gene called botR lying between the two operons in C. botulinum type A encodes an alternative sigma factor which regulates positively the synthesis of BoNT and ANTPs at the late exponential growth phase and beginning of the stationary phase. In Clostridium tetani, the gene located immediately upstream of tent encodes a positive regulatory protein, TetR, which is related to BotR. C. botulinum and C. tetani genomes contain several two-component systems and predicted regulatory orphan genes. In C. botulinum type A, four two-component systems have been found that positively or negatively regulate the synthesis of BoNT and ANTPs independently of BotR/A. The synthesis of neurotoxin in Clostridia seems to be under the control of complex network of regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Interaction of Botulinum Toxin with the Epithelial Barrier

    Directory of Open Access Journals (Sweden)

    Yukako Fujinaga

    2010-01-01

    Full Text Available Botulinum neurotoxin (BoNT is a protein toxin (~150 kDa, which possesses a metalloprotease activity. Food-borne botulism is manifested when BoNT is absorbed from the digestive tract to the blood stream and enters the peripheral nerves, where the toxin cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The initial obstacle to orally ingested BoNT entering the body is the epithelial barrier of the digestive tract. Recent cell biology and molecular biology studies are beginning to elucidate the mechanism by which this large protein toxin crosses the epithelial barrier. In this review, we provide an overview of the structural features of botulinum toxins (BoNT and BoNT complex and the interaction of these toxins with the epithelial barrier.

  19. Bupivacaine and botulinum toxin to treat comitant strabismus

    Directory of Open Access Journals (Sweden)

    Luisa Moreira Hopker

    2012-04-01

    Full Text Available PURPOSE: To evaluate the change in ocular motility and muscle thickness measured with ultrasonography after intramuscular injection of bupivacaine and botulinum toxin A. METHODS: Eight patients (five female were enrolled to measure ocular motility prior and 1, 7, 30 and 180 days after one injection of 2 ml of 1.5% bupivacaine and 2.5 U of botulinum toxin A in agonist and antagonist muscles, respectively, of eight amblyopic eyes. Muscle thickness was measured prior and on days 1, 7 and 30 after injection using 10-MHz ultrasonography (eyelid technique. RESULTS: Mean change in alignment was 10 prism diopters after 180 days (n=6. An average increase of 1.01 mm in muscle thickness was observed after 30 days of bupivacaine injection and 0.28 mm increase was observed after botulinum toxin A injection, as measured by ultrasonography. Lateral rectus muscles injected with bupivacaine had a mean increase of 1.5 mm in muscle thickness. CONCLUSION: In this study, a change in ocular motility was observed after 180 days of intramuscular injection of bupivacaine and botulinum toxin in horizontal extraocular muscles. Overall, there was an increase of muscle thickness in both botulinum toxinum A and bupivacaine injected muscles after 30 days of injection when measured by ultrasonography. This change was more pronounced on lateral rectus muscles after bupivacaine injection.

  20. Calf muscle volume estimates: Implications for Botulinum toxin treatment?

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Sonne-Holm, Stig; Thomsen, Carsten;

    2007-01-01

    An optimal botulinum toxin dose may be related to the volume of the targeted muscle. We investigated the suitability of using ultrasound and anthropometry to estimate gastrocnemius and soleus muscle volume. Gastrocnemius and soleus muscle thickness was measured in 11 cadaveric human legs, using u...

  1. Does motor performance matter in botulinum toxin efficacy for drooling?

    NARCIS (Netherlands)

    Erasmus, C.E.; Scheffer, A.R.T.; Hulst, K. van; Limbeek, J. van; Hoogen, F.J.A. van den; Rotteveel, J.J.; Jongerius, P.H.

    2011-01-01

    The aim of this study was to define factors that influence therapy outcome of submandibular botulinum toxin injections for drooling in children with cerebral palsy or mental disability. We postulated that differences in response may be explained by the variation of dysfunctions in the various

  2. Intramural injection with botulinum toxin significantly elongates the pig esophagus

    DEFF Research Database (Denmark)

    Larsen, Heidi Fhær; Jensen, Thorbjørn Søren Rønn; Rasmussen, Lars

    2013-01-01

    Surgical treatment of long-gap esophageal atresia (LGEA) is challenging. Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby causing muscle relaxation. We...

  3. Centrifugal microfluidic platform for ultrasensitive detection of Botulinum Toxin

    Science.gov (United States)

    Botulinum neurotoxin – a global public health threat and category A bioterrorism agent - is the most toxic substance known and one of the most challenging toxins to detect due to its lethality at extremely low concentrations. Hence the live-mouse bioassay because of its superior sensitivity, remains...

  4. Simultaneous and sensitive detection of six serotypes of botulinum neurotoxin using enzyme-linked immunosorbent assay-based protein antibody microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Lou, Jianlong; Jenko, Kathryn L.; Marks, James D.; Varnum, Susan M.

    2012-11-15

    Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, are a group of seven (A-G) immunologically distinct proteins and cause the paralytic disease botulism. These toxins are the most poisonous substances known to humans and are potential bioweapon agents. Therefore, it is necessary to develop highly sensitive assays for the detection of BoNTs in both clinical and environmental samples. In the present study, we have developed an ELISA-based protein antibody microarray for the sensitive and simultaneous detection of BoNT serotype A, B, C, D, E and F. With engineered high-affinity antibodies, the assays have sensitivities in buffer of 8 fM (1.2 pg/mL) for serotypes A and B, and 32 fM (4.9 pg/mL) for serotypes C, D, E, and F. Using clinical and environmental samples (serum and milk), the microarray is capable of detecting BoNT/A-F to the same levels as in standard buffer. Cross reactivity between assays for individual serotype was also analyzed. These simultaneous, rapid, and sensitive assays have the potential to measure botulinum toxins in a high-throughput manner in complex clinical or environmental samples.

  5. Detection, differentiation, and identification of botulinum neurotoxin serotypes C, CD, D, and DC by highly specific immunoassays and mass spectrometry.

    Science.gov (United States)

    Hansbauer, Eva-Maria; Skiba, Martin; Endermann, Tanja; Weisemann, Jasmin; Stern, Daniel; Dorner, Martin B; Finkenwirth, Friedrich; Wolf, Jessica; Luginbühl, Werner; Messelhäußer, Ute; Bellanger, Laurent; Woudstra, Cédric; Rummel, Andreas; Fach, Patrick; Dorner, Brigitte G

    2016-09-21

    Botulinum neurotoxin (BoNT) serotypes C and D and their mosaic variants CD and DC cause severe cases of botulism in animal husbandry and wildlife. Epidemiological data on the exact serotype or toxin variant causing outbreaks are rarely available, mainly because of their high sequence identity and the lack of fast and specific screening tools to detect and differentiate the four similar toxins. To fill this gap, we developed four highly specific sandwich enzyme-linked immunosorbent assays (ELISAs) able to detect and differentiate botulinum neurotoxins type BoNT/C, D, CD, and DC based on four distinct combinations of specific monoclonal antibodies targeting both conserved and divergent subdomains of the four toxins. Here, highly sensitive detection with detection limits between 2 and 24 pg mL(-1) was achieved. The ELISAs were extensively validated and results were compared with data obtained by quantitative real-time PCR using a panel of Clostridium botulinum strains, real sample materials from veterinary botulism outbreaks, and non-BoNT-producing Clostridia. Additionally, in order to verify the results obtained by ELISA screening, the new monoclonal antibodies were used for BoNT enrichment and subsequent detection (i) on a functional level by endopeptidase mass spectrometry (Endopep-MS) assays and (ii) on a protein sequence level by LC-MS/MS spectrometry. Based on all technical information gathered in the validation study, the four differentiating ELISAs turned out to be highly reliable screening tools for the rapid analysis of veterinary botulism cases and should aid future field investigations of botulism outbreaks and the acquisition of epidemiological data.

  6. Attomolar detection of botulinum toxin type A in complex biological matrices.

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    Karine Bagramyan

    Full Text Available BACKGROUND: A highly sensitive, rapid and cost efficient method that can detect active botulinum neurotoxin (BoNT in complex biological samples such as foods or serum is desired in order to 1 counter the potential bioterrorist threat 2 enhance food safety 3 enable future pharmacokinetic studies in medical applications that utilize BoNTs. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a botulinum neurotoxin serotype A assay with a large immuno-sorbent surface area (BoNT/A ALISSA that captures a low number of toxin molecules and measures their intrinsic metalloprotease activity with a fluorogenic substrate. In direct comparison with the "gold standard" mouse bioassay, the ALISSA is four to five orders of magnitudes more sensitive and considerably faster. Our method reaches attomolar sensitivities in serum, milk, carrot juice, and in the diluent fluid used in the mouse assay. ALISSA has high specificity for the targeted type A toxin when tested against alternative proteases including other BoNT serotypes and trypsin, and it detects the holotoxin as well as the multi-protein complex form of BoNT/A. The assay was optimized for temperature, substrate concentration, size and volume proportions of the immuno-sorbent matrix, enrichment and reaction times. Finally, a kinetic model is presented that is consistent with the observed improvement in sensitivity. CONCLUSIONS/SIGNIFICANCE: The sensitivity, specificity, speed and simplicity of the BoNT ALISSA should make this method attractive for diagnostic, biodefense and pharmacological applications.

  7. Guidelines on the use of botulinum toxin Type A

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    Shetty M

    2008-03-01

    Full Text Available Botulinum toxin is available as types A and B. These two different forms need different dosages and hence, the physician needs to be familiar with the formulations. A thorough knowledge of the anatomy and physiology of the muscles in the area to be injected is essential. Indications for botulinum toxin: Dynamic wrinkles caused by persistent muscular contractions are the main aesthetic indications for the use of Botulinum toxin. These include forehead lines, glabellar lines, crow′s feet, bunny lines, perioral wrinkles, and platysmal bands. Non-aesthetic indications include hyperhidrosis of the palms, soles and axillae. Physicians′ qualifications : Any qualified dermatologist may practice the technique after receiving adequate training in the field. This may be obtained either during post-graduation or at any workshops dedicated to this subject. Facility: Botulinum toxin can be administered in the dermatologist′s minor procedure room. Preoperative counseling and informed consent Detailed counseling with respect to the treatment, desired effects, and longevity of the results should be discussed with the patient. The patient should be given brochures to study and adequate opportunity to seek information. A detailed consent form needs to be completed by the patient. The consent form should include the type of botulinum toxin, longevity expected and possible postoperative complications. Pre- and postoperative photography is recommended. Dosage depends on the area, muscle mass, gender and other factors outlined in these guidelines. It is recommended that beginners should focus on the basic indications in the upper third of the face and that they treat the middle and lower parts of the face only after garnering adequate experience.

  8. Effect of Botulinum Toxin and Surgery among Spasmodic Dysphonia Patients.

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    van Esch, Babette F; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

    2017-02-01

    Objective The effect of botulinum toxin among patients with adductor spasmodic dysphonia (AdSD) is temporary. To optimize long-term treatment outcome, other therapy options should be evaluated. Alternative treatment options for AdSD comprise several surgical treatments, such as thyroarytenoid myotomy, thyroplasty, selective laryngeal adductor denervation-reinnervation, laryngeal nerve crush, and recurrent laryngeal nerve resection. Here, we present the first systematic review comparing the effect of botulinum toxin with surgical treatment among patients diagnosed with AdSD. Data Sources MEDLINE (PubMed), EMBASE, and the Cochrane Library. Methods Articles were reviewed by 2 independent authors, and data were compiled in tables for analysis of the objective outcome (voice expert evaluation after voice recording), the subjective outcome (patient self-assessment scores), and voice-related quality of life (Voice Health Index scores). Results No clinical trials comparing both treatment modalities were identified. Single-armed studies evaluated either the effect of botulinum toxin or surgical treatment. Thirteen studies reported outcomes after botulinum toxin treatment (n = 419), and 9 studies reported outcomes after surgical treatment (n = 585 patients). A positive effect of bilateral botulinum toxin injections was found for the objective voice outcome, subjective voice outcome, and quality of life. The duration of the beneficial effect ranged from 15 to 18 weeks. Surgical treatment had an overall positive effect on objective voice improvement, subjective voice improvement, and quality of live. Conclusion No preference for one treatment could be demonstrated. Prospective clinical trials comparing treatment modalities are recommended to delineate the optimal outcomes by direct comparison.

  9. Bone and cartilage changes in rabbit mandibular condyles after a single injection of botulinum toxin

    Science.gov (United States)

    Matthys, Tori; Ho Dang, Hong An; Rafferty, Katherine L.; Herring, Susan W.

    2015-01-01

    Introduction Temporary paralysis of the masseter muscle using botulinum toxin is a common treatment for temporomandibular disorders, bruxism, and muscle hypertrophy. Loss of masseter force is associated with decreased mandibular mineral density. Our objectives were (1) to establish whether bone loss at the mandibular condyle is regionally specific, and (2) to ascertain whether the treatment affects the condylar cartilage. Methods Young adult female rabbits received a unilateral masseter injection of botulinum neurotoxin serotype A (BoNT/A, n=31), saline (n=19) or no injection (n=3) and were also injected with bromodeoxyuridine (BrdU), a replication marker. Termination occurred 4 or 12 weeks following treatment. Condyles were processed by paraffin histology. Cortical thickness, cartilage thickness and trabecular bone areal density were measured, and replicating cells were counted after BrdU reaction. Results BoNT/A rabbits exhibited a high frequency of defects in the condylar bone surface, occurring equally on injected and uninjected sides. Bone loss was seen only on the side of the BoNT/A injection. Cortical as well as trabecular bone was severely affected. The midcondylar region lost the most bone. Recovery at 12 weeks was insignificant. Condylar cartilage thickness showed no treatment effect but did increase with time. Numbers of proliferating cells were similar in treatment groups, but BoNT/A animals showed more side asymmetry in association with the condylar defects. Conclusion Bone loss may be a risk factor for the use of botulinum toxin in jaw muscles. PMID:26672706

  10. Botulinum Toxin for the Treatment of Tremor and Tics.

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    Lotia, Mitesh; Jankovic, Joseph

    2016-02-01

    The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects.

  11. Botulinum toxin A for trismus in cephalic tetanus

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    Luiz Augusto F. Andrade

    1994-09-01

    Full Text Available Cephalic tetanus is a localized form of tetanus. As in generalized forms , trismus is a prominent feature of the disease, leading to considerable difficulty in feeding, swallowing of the saliva and mouth hygiene. These difficulties often precede respiratory problems and aspiration bronchopneumonia is a frequent life-threatening complication. Muscle relaxants other than curare drugs may show a limited benefit for relieving trismus. Tetanospasmin, the tetanic neurotoxin, and botulinum toxin share many similarities, having a closely related chemical structure, an origin from related microorganisms (Clostridium tetani and Clostridium botulinum, respectively, and presumably, the same mechanisms of action in the neuron. The difference between the two lies in their peculiar neurospecificity, acting in different neurons. Injection of minute doses of botulinum toxin in the muscles involved in focal dystonias or other localized spastic disorders have proved to be very effective in these conditions. We describe the use of botulinum toxin A in the successful treatment of trismus in a patient suffering from cephalic tetanus. We believe that this form of treatment may be of value in lowering the risk of pulmonary complications in tetanic patients.

  12. Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe?

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    Fraint A

    2016-02-01

    Full Text Available Avram Fraint,1 Padmaja Vittal,2 Cynthia Comella2 1Department of Neurological Sciences, 2Section of Movement Disorders, Rush University Medical Center, Chicago, IL, USA Introduction: Botulinum toxin (BoNT is the treatment of choice for many neurologic movement disorders, including blepharospasm, hemifacial spasm, and cervical dystonia. There are two serotypes approved for use by the US Food and Drug Administration: three brands of serotype A and one of serotype B. Many attempts have been made at establishing dose conversion ratios between brands and serotypes. This review focuses on the existing data comparing different formulations of the same BoNT serotypes as well as that comparing different serotypes with one another. We focus on existing data regarding switching from one formulation or serotype to another and will also discuss the issue of immunogenicity of BoNT. With this information as a foundation, recommendations on safety of switching agents are addressed. Method: Literature review searching PubMed and Google Scholar using the search terms “switching botox”, “dosing equivalency in botox”, and “comparing botox”. Results/conclusion: Overall, there are many studies that demonstrate the efficacy and safety of each of the brands of BoNTs used in clinical practice. However, determination of dosing equivalencies among these brands and serotypes is complex with inconsistencies among the studies. When switching from one brand to another, the clinician should be aware of these issues, and not make the assumption that such ratios exist. Tailoring the dosage of each brand of BoNT to the clinical situation is the most prudent treatment strategy rather than focusing closely on conversion factors and concerns for immunogenicity. Keywords: botulinum toxin, BoNT, abobotulinumtoxin A, onabotulinumtoxin A, incobotulinumtoxin A, rimabotulinumtoxin B

  13. The use of botulinum toxin in ophthalmology.

    Science.gov (United States)

    Denniston, A; Reuser, T

    2001-08-01

    As the diversity of clinical applications for the botulinum neurotoxin continues to grow, exciting developments are occurring in its use around the eye, where indeed its benefits were first recognized. These include use to treat strabismus, eyelid disorders and a number of other ocular conditions.

  14. Monoclonal Antibodies that Inhibit the Proteolytic Activity of Botulinum Neurotoxin Serotype/B

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    Yongfeng Fan

    2015-08-01

    Full Text Available Existing antibodies (Abs used to treat botulism cannot enter the cytosol of neurons and bind to botulinum neurotoxin (BoNT at its site of action, and thus cannot reverse paralysis. However, Abs targeting the proteolytic domain of the toxin could inhibit the proteolytic activity of the toxin intracellularly and potentially reverse intoxication, if they could be delivered intracellularly. As such, antibodies that neutralize toxin activity could serve as potent inhibitory cargos for therapeutic antitoxins against botulism. BoNT serotype B (BoNT/B contains a zinc endopeptidase light chain (LC domain that cleaves synaoptobrevin-2, a SNARE protein responsible for vesicle fusion and acetylcholine vesicle release. To generate monoclonal Abs (mAbs that could reverse paralysis, we targeted the protease domain for Ab generation. Single-chain variable fragment (scFv libraries from immunized mice or humans were displayed on yeast, and 19 unique BoNT/B LC-specific mAbs isolated by fluorescence-activated cell sorting (FACS. The equilibrium dissociation constants (KD of these mAbs for BoNT/B LC ranged from 0.24 nM to 14.3 nM (mean KD 3.27 nM. Eleven mAbs inhibited BoNT/B LC proteolytic activity. The fine epitopes of selected mAbs were identified by alanine-scanning mutagenesis, revealing that inhibitory mAbs bound near the active site, substrate-binding site or the extended substrate-binding site. The results provide mAbs that could prove useful for intracellular reversal of paralysis and identify epitopes that could be targeted by small molecules inhibitors.

  15. Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy.

    Science.gov (United States)

    Kikuchi, Akio; Takeda, Atsushi; Sugeno, Naoto; Miura, Emiko; Kato, Kazuhiro; Hasegawa, Takafumi; Baba, Toru; Konno, Masatoshi; Oshima, Ryuji; Watanuki, Shoichi; Hiraoka, Kotaro; Tashiro, Manabu; Aoki, Masashi

    2016-01-01

    We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.

  16. Botulinum toxin type A as treatment of partially accommodative esotropia.

    Science.gov (United States)

    Flores-Reyes, E M; Castillo-López, M G; Toledo-Silva, R; Vargas-Ortega, J; Murillo-Correa, C E; Aguilar-Ruiz, A

    2016-03-01

    To determine the effectiveness of a botulinum toxin type A injection in both medial rectus muscles in patients with partially accommodative esotropia. Residual deviation and stability of strabismus were evaluated at 18 months follow up. A prospective, analytical, quasi-experimental study was conducted on a cohort of 21 patients who underwent total cycloplegic refraction and with a residual deviation of at least 14 DP. A botulinum toxin type A dose of 5 IU was injected into each medial rectus muscle for a residual deviation greater than 18 DP, with a dose of 2.5 IU being used for a deviation between 14 and 18 DP. Multivariate logistic regression analyses were performed to relate residual deviation to variables recorded as potential predictors. A total of 21 patients were included, 33.3% (n=7) males and 66.6% (n=14) females. Mean visual acuity was -.28±.25 logMAR for right eye (range 0 to -1) and -.42±.31 logMAR for left eye (range 0 to -1.3). Mean angle of residual deviation before application of botulinum toxin was 40.95±8.6DP without spectacles correction, and 22.3±7.99 DP with full cycloplegic refraction. Adverse effects were ptosis in 14.2% (n=3), diplopia 23.8% (n=5), and vertical deviation in 33% (n=7). One patient had a poor outcome, therefore required surgical treatment. At one year follow up, 85.71% of patients showed good results with esotropia of 12 DP or less, dropping to 71.43% at 18 months of follow up. Botulinum toxin type A is an effective long-term treatment with a good response in 71.43% of patients. No predictors of good response were demonstrated. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Botulinum toxin: An emerging therapy in female bladder outlet obstruction

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    Aditya A Pradhan

    2009-01-01

    Discussion: There is a gradual improvement in symptoms over time and the maximal effect occurred at 10-14 days. The duration of improvement was approximately 16.8 weeks. All patients were satisfied by the degree of improvement felt. Conclusions: Botulinum toxin proved successful in improving the voiding characteristics. It possibly acts at the zone of hypertonicity at the bladder neck or midurethra. The only disadvantage is the high cost of the drug.

  18. A Beautician's Dystonia: Long-Lasting Effect of Botulinum Toxin

    Science.gov (United States)

    Di Martino, Siria; Dalise, Stefania; Lamola, Giuseppe; Venturi, Martina; Rossi, Bruno; Chisari, Carmelo

    2014-01-01

    Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders). Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin) into the extensor digitorum communis (35 U), flexor carpi radialis (35 U), and flexor digitorum superficialis (30 U) muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment). In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients' ability to work and quality of life. PMID:25143844

  19. Botulinum toxin A in the treatment of anal fissure

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    Stanković Nebojša

    2004-01-01

    Full Text Available Background. This paper presents our first experience in the treatment of primary anal fissure by injection of botulinum A toxin into the internal sphincter. Methods. The study group of the retrospective study included 12 outpatients (8 females and 4 males, mean age 42 (range 18-60. During the period 2000-2003, after unsuccessful conservative treatment, patients were treated with the injections of botulinum A toxin, 100 units on both sides of the anal fissure laterally into the internal anal sphincter (50 units on either side. The patients were clinically evaluated 3, 7, and 30 days, and 3 and 6 months after the treatment. Results. Three fissures had healed after a month, and seven after 3 months. Two remained unhealed, but asymptomatic. There was no incontinence of flatus or faeces after 3 months of the treatment. After temporary healing, two fissures relapsed after 6 months, and these patients had the adequate tonus of the anal sphincter muscles. Except for the temporary incontinence, there were neither other side-efects, nor serious complications. Conclusion. Injection of botulinum A toxin achieved good results in the treatment of anal fissure. The appropriate use makes this method safe as an alternative to surgical treatment of anal fissure.

  20. Zebrafish (Danio rerio) bioassay for visceral toxicosis of catfish and botulinum neurotoxin serotype E

    Science.gov (United States)

    Visceral toxicosis of catfish (VTC), a sporadic disease of cultured channel catfish (Ictalurus punctatus) often with high mortality, is caused by botulinum neurotoxin serotype E (BoNT/E). Presumptive diagnosis of VTC is based on characteristic clinical signs and lesions, and the production of these ...

  1. Enhancing the Pharmacokinetic Properties of Botulinum Neurotoxin Serotype A Protease Inhibitors Through Rational Design.

    Science.gov (United States)

    Capek, Petr; Zhang, Yan; Barlow, Deborah J; Houseknecht, Karen L; Smith, Garry R; Dickerson, Tobin J

    2011-06-15

    Botulinum neurotoxin (BoNT), the etiological agent that causes the neuroparalytic disease botulism, has become a highly studied drug target in light of the potential abuse of this toxin as a weapon of bioterrorism. In particular, small molecule inhibitors of the light chain metalloprotease of BoNT serotype A have received significant attention and a number of small molecule and biologic inhibitors have been reported. However, all small molecules reported have been identified from either primary screens or medicinal chemistry follow-up studies, and the pharmacokinetic profiles of these compounds have not been addressed. In this study, we have removed the pharmacologic liabilities of one of the best compounds reported to date, 2,4-dichlorocinnamate hydroxamic acid, and in the process, uncovered a related class of benzothiophene hydroxamic acids that are significantly more potent inhibitors of the BoNT/A light chain, while also possessing greatly improved ADME properties, with the best compound showing the most potent inhibition of BoNT/A light chain reported (K(i) = 77 nM). Using a strategy of incorporating traditional drug development filters early into the discovery process, potential liabilities in BoNT/A lead compounds have been illuminated and removed, clearing the path for advancement into further pharmacologic optimization and in vivo efficacy testing.

  2. A double-blind, randomised, crossover trial of two botulinum toxin type a in patients with spasticity.

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    Fábio Coelho Guarany

    Full Text Available BACKGROUND: Botulinum toxin type A (btxA is one of the main treatment choices for patients with spasticity. Prosigne® a new released botulinum toxin serotype A may have the same effectiveness as Botox® in focal dystonia. However, there are no randomized clinical trials comparing these formulations in spasticity treatment. The aim of our study was to compare the efficacy and safety of Prosigne® with Botox® in the treatment of spasticity. METHODOLOGY/PRINCIPAL FINDINGS: We performed a double-blind, randomized, crossover study consisting of 57 patients with clinically meaningful spasticity. The patients were assessed at baseline, 4 and 12 weeks after Prosigne® or Botox® administration. The main outcomes were changes in the patients' Modified Ashworth Scale (MAS, Functional Independence Measure (FIM and Pediatric Evaluation of Disability Inventory (PEDI scores and adverse effects related to the botulinum toxin. Both of the toxins were significantly effective in relieving the level of spasticity in adults and children. There were no significant differences found between the Prosigne® and Botox® treatments regarding their MAS, FIM and PEDI scores. Likewise, the incidence of adverse effects was similar between the two groups. CONCLUSION: Our results suggest that Prosigne® and Botox® are both efficient and comparable with respect to their efficacy and safety for the three month treatment of spasticity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00819065.

  3. Comparative sequence analyses of the neurotoxin complex genes in Clostridium botulinum serotypes A, B, E, and F

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    Ajay K. Singh

    2012-09-01

    Full Text Available Neurotoxin complex (NTC genes are arranged in two known hemagglutinin (HA and open reading frame X (ORFX clusters. NTC genes have been analyzed in four serotypes A, B, E and F of Clostridium botulinum causing human botulism. Analysis of amino acid sequences of NT genes demonstrated significant differences among subtypes and four serotypes. Phylogram tree of NT genes reveals that serotypes A1 and B1 are much closer compared to serotype E1 and F1. However, non-toxic non-hemagglutinin (NTNH gene is highly conserved among four serotypes. Analysis of phylogram tree of NTNH gene reveals that serotypes A and F are more closely related compared to serotype B and E. Additionally, sequences of HAs and ORFX genes are very divergent but these genes are specific in subtypes and serotypes of Clostridium botulinum. Information derived from sequence analyses of NTC has direct implication in development of detection tools and therapeutic countermeasures for botulism.

  4. Does vitamin B alter the efficacy of botulinum toxin?

    Science.gov (United States)

    Tatlidede, Soner; Baslo, M Baris; Özkaya, Özay; Soydan, Tufan; Orhan, Elif Kocasoy; Yeşilada, Ayşin Karasoy

    2012-06-01

    Botulinum toxin prevents acetylcholine release at motor nerve terminals. Group B vitamins (B-vit) are essential for proper nerve function. The present study addresses the question of whether B-vit accelerate recovery in rat skeletal muscle after botulinum toxin A (Btx-A) injection. Forty-four adult male Wistar albino rats were used in this experimental study. Rats were divided into three groups: group 1 rats were given Btx-A injection only, group 2 rats were given B-vit supplementation before Btx-A injection, and group 3 rats were given Btx-A and B-vit injections together. During the experiment, compound muscle action potential (CMAP) of the gastrocnemius muscle was recorded before Btx-A injection and sequentially ten times after toxin injection. The statistical significance of the CMAP amplitude change among the groups was analyzed. All groups showed similar amplitude change between consecutive measurement points. In conclusion, combining Btx-A injection with B-vit supplement does not decrease the efficacy of the toxin.

  5. High-throughput enzyme-linked immunoabsorbant assay (ELISA) electrochemiluminescent detection of botulinum toxins in foods for food safety and defence purposes.

    Science.gov (United States)

    Phillips, R W; Abbott, D

    2008-09-01

    Clostridum species produce seven serotypes (A-G) of botulinum toxin, four of which (A, B, E, and F) are normally associated with human illness. To date, the most reliable test for botulinum toxin is the mouse bioassay. The authors' laboratory has been exploring the use of an antibody-based assay similar to an enzyme-linked immunoabsorbant assay (ELISA) but utilizing electrochemiluminescent technology (BioVerify assay) as an alternative to the mouse bioassay for testing food samples. The detection limit of this assay is as low as 10 ng g(-1) depending on the food matrix and the serotype detected. Detection of botulinum toxin between 10 and 200 ng g(-1) is a linear curve allowing for the possibility of performing quantitative as well as qualitative testing of samples. The ease of the assay, limited sample preparation, and low detection limit make the BioVerify assay and instrument an excellent, high-throughput option for detecting botulinum toxins in food matrices.

  6. Prevention of arterial graft spasm by botulinum toxin: an in-vitro experiment.

    Science.gov (United States)

    Murakami, Eiji; Iwata, Hisashi; Imaizumi, Matsuhisa; Takemura, Hirohumi

    2009-09-01

    In coronary artery bypass surgery, arterial grafts result in improved patency rates. However, these grafts frequently fail due to spasm. Papaverine has been used to prevent graft spasm, but its effect is short-lived. Botulinum toxin inhibits muscle contraction for about three months. We investigated the usefulness of botulinum toxin in preventing arterial grafts spasm in vitro. Samples of abdominal aorta from male Wistar rats were cut into 2 mm rings and treated with various doses of botulinum toxin or papaverine for 30 min. All rings were stimulated with KCl and noradrenaline. Tension was recorded using myography. We compared constriction caused by noradrenaline or KCl in rings treated with botulinum toxin, or papaverine, or physiological salt solution (PSS) (control). In the presence of KCl and noradrenaline, almost all concentrations of botulinum toxin completely inhibited arterial contraction when compared with controls. Spasm prevention was lost after 60 min in rings with papaverine but persisted for 120 min in rings with botulinum toxin. In the histological examination, arterial wall structure was not destroyed by botulinum toxin. Botulinum toxin prevented arterial graft spasm in vitro and had a longer lasting effect than papaverine, with no toxic effect on the artery.

  7. Acute deterioration of bulbar function after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Meijer, J.W.; Kuijk, A.A. van; Geurts, A.C.H.; Schelhaas, H.J.; Zwarts, M.J.

    2008-01-01

    Transcutaneous botulinum toxin injection in the salivary glands was introduced in 2000 as a new treatment for sialorrhoea in amyotrophic lateral sclerosis (ALS). We describe an ALS patient who developed serious complications of botulinum toxin treatment for sialorrhoea, and we review the relevant li

  8. Utilization of quail and chicken embryos for the detection of botulinum toxin type A activity

    Science.gov (United States)

    Clostridium botulinum is a ubiquitous microorganism which can produce botulinum toxins and the ability to assess toxin activity in a food sample is critical. As an alternative to the mouse assay incubating quail (Coturnix coturnix japonica) and chicken (Gallus gallus domestics) embryos were evaluat...

  9. Muscle selection for treatment of cervical dystonia with botulinum toxin : A systematic review

    NARCIS (Netherlands)

    Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

    2012-01-01

    Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be selecte

  10. Use of Clostridium botulinum toxin in gastrointestinalmotility disorders in children

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    More than a century has elapsed since the identificationof Clostridia neurotoxins as the cause of paralyticdiseases. Clostridium botulinum is a heterogeneousgroup of Gram-positive, rod-shaped, spore-forming,obligate anaerobic bacteria that produce a potentneurotoxin. Eight different Clostridium botulinumneurotoxins have been described (A-H) and 5 of thosecause disease in humans. These toxins cause paralysisby blocking the presynaptic release of acetylcholine atthe neuromuscular junction. Advantage can be taken ofthis blockade to alleviate muscle spams due to excessiveneural activity of central origin or to weaken a musclefor treatment purposes. In therapeutic applications,minute quantities of botulinum neurotoxin type A areinjected directly into selected muscles. The Food andDrug Administration first approved botulinum toxin (BT)type A in 1989 for the treatment of strabismus andblepharospasm associated with dystonia in patients 12years of age or older. Ever since, therapeutic applicationsof BT have expanded to other systems, including thegastrointestinal tract. Although only a single fatalityhas been reported to our knowledge with use of BTfor gastroenterological conditions, there are significantcomplications ranging from minor pain, rash and allergicreactions to pneumothorax, bowel perforation andsignificant paralysis of tissues surrounding the injection(including vocal cord paralysis and dysphagia). Thiseditorial describes the clinical experience and evidencefor the use BT in gastrointestinal motility disorders inchildren.

  11. Can botulinum toxin put the restless legs syndrome to rest?

    Science.gov (United States)

    Lim, Erle C H; Seet, Raymond C S

    2007-01-01

    The restless legs syndrome (RLS), affecting between 3% and 15% of the population, is characterised by an urge to move the legs during wakefulness, associated with a range of unpleasant sensory symptoms, especially when sitting or lying down at night. The symptoms can even be painful, and lead to sleep disturbances and depression. RLS is treated with dopaminergic agents, anticonvulsants, opioids, clonidine and benzodiazepines. In a small percentage of cases, RLS is refractory to treatment, requiring combination therapy. Botulinum toxin (BTX), derived from the exotoxin of Clostridium botulinum, cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, causing chemodenervation of cholinergic neurons. BTX has been demonstrated to ameliorate pain syndromes, possibly by reducing peripheral and central sensitization to pain. We postulate that BTX can be injected subcutaneously to the lower limbs to effect amelioration of the symptoms of RLS.

  12. High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex

    Science.gov (United States)

    Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna Magdalena; Perry, Kay; Rummel, Andreas; Jin, Rongsheng

    2014-01-01

    Botulinum neurotoxins (BoNTs) are produced as progenitor toxin complexes (PTCs) by Clostridium botulinum. The PTCs are composed of BoNT and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver BoNT through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich PTC on the intestinal lumen preceding its transport across the epithelial barriers. Here, we report the crystal structure of HA33 of type B PTC (HA33/B) in complex with lactose at 1.46 Å resolution. The structural comparisons among HA33 of serotypes A–D reveal two different HA33–glycan interaction modes. The glycan-binding pockets on HA33/A and B are more suitable to recognize galactose-containing glycans in comparison to the equivalent sites on HA33/C and D. On the contrary, HA33/C and D could potentially recognize Neu5Ac as an independent receptor, whereas HA33/A and B do not. These findings indicate that the different oral toxicity and host susceptibility observed among different BoNT serotypes could be partly determined by the serotype-specific interaction between HA33 and host carbohydrate receptors. Furthermore, we have identified a key structural water molecule that mediates the HA33/B–lactose interactions. It provides the structural basis for development of new receptor-mimicking compounds, which have enhanced binding affinity with HA33 through their water-displacing moiety. PMID:24631690

  13. Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin

    Directory of Open Access Journals (Sweden)

    Masaya Takehara

    2017-08-01

    Full Text Available Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

  14. Crystal Structure of Botulinum Neurotoxin Type a in Complex With the Cell Surface Co-Receptor GT1b-Insight Into the Toxin-Neuron Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, P.; Dupuy, J.; Inamura, A.; Kiso, M.; Stevens, R.C.

    2009-05-26

    Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

  15. Identification and genetic characterization of Clostridium botulinum serotype A strains from commercially pasteurized carrot juice.

    Science.gov (United States)

    Marshall, Kristin M; Nowaczyk, Louis; Raphael, Brian H; Skinner, Guy E; Rukma Reddy, N

    2014-12-01

    Clostridium botulinum is an important foodborne pathogen capable of forming heat resistant endospores and producing deadly botulinum neurotoxins (BoNTs). In 2006, C. botulinum was responsible for an international outbreak of botulism attributed to the consumption of commercially pasteurized carrot juice. The purpose of this study was to isolate and characterize strains of C. botulinum from the adulterated product. Carrot juice bottles retrieved from the manufacturing facility were analyzed for the presence of BoNT and BoNT-producing isolates using DIG-ELISA. Toxigenic isolates from the carrot juice were analyzed using pulsed-field gel electrophoresis (PFGE) and DNA microarray analysis to determine their genetic relatedness to the original outbreak strains CDC51348 and CDC51303. PFGE revealed that isolates CJ4-1 and CJ10-1 shared an identical pulsotype with strain CDC51303, whereas isolate CJ5-1 displayed a unique restriction banding pattern. DNA microarray analysis identified several phage related genes unique to strain CJ5-1, and Southern hybridization analysis of XhoI digested and nondigested DNA showed their chromosomal location, while a homolog to pCLI_A009 of plasmid pCLI of C. botulinum serotype Langeland F, was located on a small plasmid. The acquisition or loss of bacteriophages and other mobile genetic elements among C. botulinum strains has epidemiological and evolutionary implications.

  16. In Silico Analysis for the Study of Botulinum Toxin Structure

    Science.gov (United States)

    Suzuki, Tomonori; Miyazaki, Satoru

    2010-01-01

    Protein-protein interactions play many important roles in biological function. Knowledge of protein-protein complex structure is required for understanding the function. The determination of protein-protein complex structure by experimental studies remains difficult, therefore computational prediction of protein structures by structure modeling and docking studies is valuable method. In addition, MD simulation is also one of the most popular methods for protein structure modeling and characteristics. Here, we attempt to predict protein-protein complex structure and property using some of bioinformatic methods, and we focus botulinum toxin complex as target structure.

  17. Advances in Assays and Analytical Approaches for Botulinum Toxin Detection

    Energy Technology Data Exchange (ETDEWEB)

    Grate, Jay W.; Ozanich, Richard M.; Warner, Marvin G.; Bruckner-Lea, Cindy J.; Marks, James D.

    2010-08-04

    Methods to detect botulinum toxin, the most poisonous substance known, are reviewed. Current assays are being developed with two main objectives in mind: 1) to obtain sufficiently low detection limits to replace the mouse bioassay with an in vitro assay, and 2) to develop rapid assays for screening purposes that are as sensitive as possible while requiring an hour or less to process the sample an obtain the result. This review emphasizes the diverse analytical approaches and devices that have been developed over the last decade, while also briefly reviewing representative older immunoassays to provide background and context.

  18. Botulinum toxin: examining duration of effect in facial aesthetic applications.

    Science.gov (United States)

    Flynn, Timothy Corcoran

    2010-01-01

    Patient satisfaction with botulinum toxin treatment is a key success factor in aesthetic procedures and is governed by the interaction of numerous variables. Duration of effect is important because it influences retreatment intervals as well as affecting cost and convenience to the patient. In order to review the evidence on the duration of benefit associated with various commercial formulations of botulinum toxin, MEDLINE was searched using the following terms: 'botulinum' and 'duration'/'retreatment' (limits: 'clinical trials,' 'meta-analyses,' 'English'). I also searched my existing reference files, reference lists of identified articles, and meeting/conference abstracts to ensure completeness. The focus was on clinical medicine and aesthetic trials. To be eligible for the analysis, studies had to include efficacy assessments at multiple timepoints. To estimate duration of benefit, the following outcomes were examined and summarized: responder rates, mean wrinkle severity scores at various timepoints (with or without changes from baseline), and relapse rates. Duration at both repose and maximum attempted muscle contraction was considered when provided. Where possible, duration was assessed by formulation and dose. The initial search yielded 164 articles. Of these, 35 included an adequate measure of duration in aesthetic indications. The majority of these (22) were on the glabellar area. Study designs and endpoints were highly heterogeneous, and duration of effect varied between studies. Several studies with the BOTOX Cosmetic (onabotulinumtoxinA; Allergan, Inc., Irvine, CA, USA) formulation of botulinum toxin type A (BoNTA) included relapse rates, defined conservatively as return to baseline levels of line severity for two consecutive visits approximately 30 days apart (at repose and maximum contraction). In these studies, duration of effect ranged from 3 to 5 months in female patients and from 4 to 6 months in male patients. Individual patients had longer

  19. Evidence that plasmid-borne botulinum neurotoxin type B genes are widespread among Clostridium botulinum serotype B strains.

    Directory of Open Access Journals (Sweden)

    Giovanna Franciosa

    Full Text Available BACKGROUND: Plasmids that encode certain subtypes of the botulinum neurotoxin type B have recently been detected in some Clostridium botulinum strains. The objective of the present study was to investigate the frequency with which plasmid carriage of the botulinum neurotoxin type B gene (bont/B occurs in strains of C. botulinum type B, Ab, and A(B, and whether plasmid carriage is bont/B subtype-related. METHODOLOGY/PRINCIPAL FINDINGS: PCR-Restriction fragment length polymorphism was employed to identify subtypes of the bont/B gene. Pulsed-field gel electrophoresis and Southern blot hybridization with specific probes were performed to analyze the genomic location of the bont/B subtype genes. All five known bont/B subtype genes were detected among the strains; the most frequently detected subtype genes were bont/B1 and /B2. Surprisingly, the bont/B subtype gene was shown to be plasmid-borne in >50% of the total strains. The same bont/B subtype gene was associated with the chromosome in some strains, whereas it was associated with a plasmid in others. All five known bont/B subtype genes were in some cases found to reside on plasmids, though with varying frequency (e.g., most of the bont/B1 subtype genes were located on plasmids, whereas all but one of the bont/B2 subtypes were chromosomally-located. Three bivalent isolates carried both bont/A and /B genes on the same plasmid. The plasmids carrying the bont gene were five different sizes, ranging from approximately 55 kb to approximately 245 kb. CONCLUSIONS/SIGNIFICANCE: The unexpected finding of the widespread distribution of plasmids harboring the bont/B gene among C. botulinum serotype B strains provides a chance to examine their contribution to the dissemination of the bont genes among heterogeneous clostridia, with potential implications on issues related to pathogenesis and food safety.

  20. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin.

    Science.gov (United States)

    Erbguth, Frank J

    2004-03-01

    Food-borne botulism probably has accompanied mankind since its beginning. However, we have only few historical sources and documents on food poisoning before the 19th century. Some ancient dietary laws and taboos may reflect some knowledge about the life-threatening consumption of poisoned food. One example of such a dietary taboo is the 10th century edict of Emperor Leo VI of Byzantium in which manufacturing of blood sausages was forbidden. Some ancient case reports on intoxications with Atropa belladonna probably described patients with food-borne botulism, because the combination of dilated pupils and fatal muscle paralysis cannot be attributed to an atropine intoxication. At the end of the 18th century, some well-documented outbreaks of "sausage poisoning" in Southern Germany, especially in Württemberg, prompted early systematic botulinum toxin research. The German poet and district medical officer Justinus Kerner (1786-1862) published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822. Kerner did not succeed in defining the suspected "biological poison" which he called "sausage poison" or "fatty poison." However, he developed the idea of a possible therapeutic use of the toxin. Eighty years after Kerner's work, in 1895, a botulism outbreak after a funeral dinner with smoked ham in the small Belgian village of Ellezelles led to the discovery of the pathogen Clostridium botulinum by Emile Pierre van Ermengem, Professor of bacteriology at the University of Ghent. The bacterium was so called because of its pathological association with the sausages (Latin word for sausage = "botulus") and not-as it was suggested-because of its shape. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz. Copyright 2004 Movement Disorder Society

  1. Characterisation of botulinum toxins type A and B, by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

    NARCIS (Netherlands)

    Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

    2002-01-01

    A method earlier developed for the mass spectrometric (MS) identification of tetanus toxin (TTx) was applied to botulinum toxins type A and B (BTxA and BTxB). Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. Biologically active BTxA and BTxB

  2. Characterisation of botulinum toxins type A and B, by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

    NARCIS (Netherlands)

    Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

    2002-01-01

    A method earlier developed for the mass spectrometric (MS) identification of tetanus toxin (TTx) was applied to botulinum toxins type A and B (BTxA and BTxB). Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. Biologically active BTxA and BTxB

  3. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin.

    Science.gov (United States)

    Koh, Chung-Yan; Schaff, Ulrich Y; Piccini, Matthew E; Stanker, Larry H; Cheng, Luisa W; Ravichandran, Easwaran; Singh, Bal-Ram; Sommer, Greg J; Singh, Anup K

    2015-01-20

    We present an innovative centrifugal microfluidic immunoassay platform (SpinDx) to address the urgent biodefense and public health need for ultrasensitive point-of-care/incident detection of botulinum toxin. The simple, sample-to-answer centrifugal microfluidic immunoassay approach is based on binding of toxins to antibody-laden capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by laser-induced fluorescence. A blind, head-to-head comparison study of SpinDx versus the gold-standard mouse bioassay demonstrates 100-fold improvement in sensitivity (limit of detection = 0.09 pg/mL), while achieving total sample-to-answer time of capture beads and detection antibodies) are disconnected from the disk architecture and the reader, facilitating rapid development of new assays. SpinDx can also serve as a general-purpose immunoassay platform applicable to diagnosis of other conditions and diseases.

  4. Zebrafish (Danio rerio) bioassay for visceral toxicosis of catfish and botulinum neurotoxin serotype E.

    Science.gov (United States)

    Chatla, Kamalakar; Gaunt, Patricia; Petrie-Hanson, Lora; Hohn, Claudia; Ford, Lorelei; Hanson, Larry

    2014-03-01

    Visceral toxicosis of catfish (VTC), a sporadic disease of cultured channel catfish (Ictalurus punctatus) often with high mortality, is caused by botulinum neurotoxin serotype E (BoNT/E). Presumptive diagnosis of VTC is based on characteristic clinical signs and lesions, and the production of these signs and mortality after sera from affected fish is administered to sentinel catfish. The diagnosis is confirmed if the toxicity is neutralized with BoNT/E antitoxin. Because small catfish are often unavailable, the utility of adult zebrafish (Danio rerio) was evaluated in BoNT/E and VTC bioassays. Channel catfish and zebrafish susceptibilities were compared using trypsin-activated BoNT/E in a 96-hr trial by intracoelomically administering 0, 1.87, 3.7, 7.5, 15, or 30 pg of toxin per gram of body weight (g-bw) of fish. All of the zebrafish died at the 7.5 pg/g-bw and higher, while the catfish died at the 15 pg/g-bw dose and higher. To test the bioassay, sera from VTC-affected fish or control sera were intracoelomically injected at a dose of 10 µl per zebrafish and 20 µl/g-bw for channel catfish. At 96 hr post-injection, 78% of the zebrafish and 50% of the catfish receiving VTC sera died, while no control fish died. When the VTC sera were preincubated with BoNT/E antitoxin, they became nontoxic to zebrafish. Histology of zebrafish injected with either VTC serum or BoNT/E demonstrated renal necrosis. Normal catfish serum was toxic to larval zebrafish in immersion exposures, abrogating their utility in VTC bioassays. The results demonstrate bioassays using adult zebrafish for detecting BoNT/E and VTC are sensitive and practical.

  5. Botulinum Toxin A in Treatment of Facial Flushing

    Directory of Open Access Journals (Sweden)

    Gholamreza Eshghi

    2016-07-01

    Full Text Available Flushing is a condition with episodic attacks of redness of the skin with a sensation of warmth or burning, this disease causes emotional and functional problems in patients. There is various treatments for this condition; one of them is the use of botulinum toxin-A (BTA. In this prospective pilot study we studied the effect of Botulinum toxin-A (BTA effect on DLQI of patients with facial flushing, we compared the DLQI before and after treatment. The number of 24 women with facial flushing admitted to the department of dermatology of Hamadan Farshchian Hospital, with the age range of 18 to 60 was enrolled in the study. Patients completed Dermatology Quality of life Index questionnaire before and one month after treatment. In our study 1 unit of BTA was injected intracutaneously per square cm in both sides of cheeks, to a total dose of 30 units per session. All of 24 patients completed the study. The mean age was 37.79±13.13. In all patients, DLQI decreased, and in two months follow up, the mean of DLQI improved from 8.08±1.17 to 4.5±1.21 (P.value<0.005. Based on this study BTA is an effective and safe treatment for facial flushing.

  6. Botulinum toxin (Botox) to enhance facial macroesthetics: a literature review.

    Science.gov (United States)

    Dastoor, Sarosh F; Misch, Carl E; Wang, Hom-Lay

    2007-01-01

    Dental implants have emerged as a predictable treatment option for partial edentulism. Their ability to preserve bone and soft tissue yields highly esthetic results in the long term. Increasingly, patients are demanding not only enhancements to their dental (micro) esthetics but also to their overall facial (macro) esthetics. Dynamic wrinkles (caused by hyperfunctional muscles) in the perioral, glabellar, and forehead regions can cause a patient's expressions to be misinterpreted as angry, anxious, fearful, or fatigued. An emerging treatment option to address these issues is the use of a paralyzing material such as botulinum toxin A (Botox) to decrease the appearance of the wrinkles, which yields a more esthetic and youthful facial appearance. Botox is a deadly poison that is produced by the bacterium Clostridium botulinum and causes muscle paralysis by inhibiting acetylcholine release at the neuromuscular junction. When used in areas of hyperfunctional muscles, a transient partial paralysis occurs that diminishes the appearances of wrinkles, Therefore, wrinkles not attributable to hyperfunctional muscles (e.g., wrinkles caused by aging, gravity, photodamage, trauma, and scarring) will not be amenable to treatment with the toxin. As a result, proper case selection is essential. A thorough understanding of the indications, techniques, dosages, and complications and their management is imperative to achieve a satisfactory result. This article will review the pathogenesis of facial wrinkles as well as the history, techniques, clinical controversies, and other important considerations for successful treatment of facial wrinkles with Botox.

  7. Use of Botulinum toxin in 55 children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Mohammadi M

    2000-10-01

    Full Text Available Botulinum toxin A (BTA inhibits presynaptic release of acetylcholine at the neuromuscular junction and has reportedly been successful in the treatment of spastic disorders.To evaluate the effect of botulinum toxin on cerebral palsied children with spastic or mixed type of the disease, especially those patiens having spasticity as a cardinal symptom without joint contracture, we designed the following study. Ninety-one cases (55 of referred patients to pediatic Neurology outpatient clinics of children’s Medical Center were given BTA injections in affected muscles of the lower limb. They were reevaluating 3 to 5 weeks and 3 months later for type of walking and range of affected joints’ movement. The study showed a clinically significant gait improvement in 71.2% of patients (P<0.0005 and also an overall increased range of motion in affected limbs after BTA injection (P<0.04. Side effects occurred only in two cases as transient generalized weakness, gent recurvatum and ptosis. Drug effectiveness was time-limited, lasting abot 3 months in all patients ( a golden time for rehabilitation therapists to improve the patients’ condition. Overall, BTA has improved both the type of walking as well as the range of joints motion in our patients. So its’ administration is suggested in cerebral palsied children if the spasticity is a major and disabling sign

  8. Severe compensatory hyperhidrosis following thoracic sympathectomy successfully treated with low doses of botulinum toxin A.

    Science.gov (United States)

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Calatayud-Gastardi, Joaquín; García-Castellano, José Manuel; Ponce-González, Miguel A; Olmo-Quintana, Vicente; Llontop, Pedro; Alvarez-Prats, Alejandro; Yordi, Nagib Atallah; Ruíz-Caballero, José Antonio

    2012-12-01

    Compensatory hyperhidrosis is an adverse effect of thoracic sympathectomy that can be debilitating, which is why an efficient treatment is demanded. Botulinum toxin is an emerging treatment, not well known yet. We report two cases of compensatory hyperhidrosis following thoracic sympathectomy which were both treated with low doses of botulinum toxin A. The patients, a male and a female, noted a high level of satisfaction with the abolishment of sweating that was maintained up to 10 months. We consider that low doses of botulinum toxin A is a well tolerated, safe and effective treatment for compensatory hyperhidrosis and should be offered as an alternative treatment.

  9. Isolation of botulinolysin, a thiol-activated hemolysin, from serotype D Clostridium botulinum: A species-specific gene duplication in Clostridia.

    Science.gov (United States)

    Suzuki, Tomonori; Nagano, Thomas; Niwa, Koichi; Mutoh, Shingo; Uchino, Masataka; Tomizawa, Motohiro; Sagane, Yoshimasa; Watanabe, Toshihiro

    2016-12-01

    Botulinolysin (BLY) is a toxin produced by Clostridium botulinum that belongs to a group of thiol-activated hemolysins. In this study, a protein exhibiting hemolytic activity was purified from the culture supernatant of C. botulinum serotype D strain 4947. The purified protein displayed a single band by sodium dodecyl sulfate polyacrylamide gel electrophoresis with a molecular mass of 55kDa, and its N-terminal and internal amino acid sequences exhibited high similarity to a group of thiol-activated hemolysins produced by gram-positive bacteria. Thus, the purified protein was identified as the BLY. Using the nucleotide sequences of previously cloned genes for hemolysins, two types of genes encoding BLY-like proteins were cloned unexpectedly. Molecular modeling analysis indicated that the products of both genes displayed very similar structures, despite the low sequence similarity. In silico screening revealed a specific duplication of the hemolysin gene restricted to serotypes C and D of C. botulinum and their related species among thiol-activated hemolysin-producing bacteria. Our findings provide important insights into the genetic characteristics of pathogenic bacteria.

  10. Role of Botulinum Toxin Type-A (BTX-A) in the Management of Trigeminal Neuralgia

    National Research Council Canada - National Science Library

    Verma, Gaurav

    2013-01-01

    .... Newer methods were tried in search of permanent cure or long-lasting pain relief. The purpose of this paper is to present the review of the literature regarding the use of botulinum toxin type-A (BTX...

  11. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke: Case Series.

    Science.gov (United States)

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-08-01

    Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases.This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance.During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization.The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia.

  12. Botulinum toxin injection improved voluntary motor control in selected patients with post-stroke spasticity

    Institute of Scientific and Technical Information of China (English)

    Shuo-Hsiu Chang; Gerald E Francisco; Sheng Li

    2012-01-01

    The effect of botulinum toxin type A injection on voluntary grip control was examined in a 53-year-old female, who sustained a hemorrhagic right middle cerebral artery stroke 3 years previously, which resulted in finger flexor spasticity and residual weak finger/wrist extension. The patient received 50 units of botulinum toxin type A injection each to the motor points (2 sites/muscle) of the left flexor digitorum superficialis and flexor digitorum profundus, respectively. Botulinum toxin injection led to weakness and tone reduction in the spastic finger flexors, but improved grip release time in grip initiation/release reaction time tasks. Improved release time was accompanied by shortened extensor electromyography activity, and improved release time likely correlated with blocked co-contraction of finger flexors during voluntary finger extension. This case report demonstrated that botulinum toxin injection improved voluntary motor control of the hand in a chronic stroke patient with residual finger extension.

  13. Ranula successfully treated by botulinum toxin type A: report of 3 cases.

    Science.gov (United States)

    Chow, Tam-Lin; Chan, Sharon W W; Lam, Siu-Ho

    2008-01-01

    The conventional treatment of ranula is surgical procedure. We report an innovative method for ranula by using botulinum toxin type A on 3 patients. All 3 cases of ranula resolved after this minimally invasive therapy. The treatment complication was minimal.

  14. Presence of Clostridium botulinum and botulinum toxin in milk and udder tissue of dairy cows with suspected botulism.

    Science.gov (United States)

    Böhnel, H; Gessler, F

    2013-04-13

    Clostridium botulinum is an anaerobic spore-forming bacterium prevalent in the environment, and causes botulism in man and animals via toxins. Dairy cattle may be contaminated or infected by feed, water or other environmental factors. Milk may also carry the pathogen. Hence, milk and udder samples need to be tested. The number of clinical cases of bovine botulism in Germany has been increasing since the mid-1990s. Besides routine samples, additional 99 milk samples from 37 farms, and 51 udder samples from 51 farms from sick animals presumably affected by botulism were tested microbiologically by the mouse bioassay. Milk from three farms (8.1 per cent) contained botulinum toxin, and from two (5.4 per cent) bacterial states of C botulinum. Ten udder samples (19.6 per cent) contained toxin, and 7 (13.7 per cent) bacterial forms, including one case where both toxin and bacteria were found. The findings are discussed. Positive milk samples containing botulinum toxin or bacteria raise concern of food safety for the human consumer. Pathological udder samples may show either infection prior to, or contamination after death.

  15. Bruxism secondary to brain injury treated with Botulinum toxin-A: a case report

    Science.gov (United States)

    El Maaytah, Mohammed; Jerjes, Waseem; Upile, Tahwinder; Swinson, Brian; Hopper, Colin; Ayliffe, Peter

    2006-01-01

    We report a successful treatment of bruxism in a patient with anoxic brain injury using botulinum toxin-A (BTX-A). On examination the mouth opening was 0 mm, no feeding was possible through the mouth. Botulinum toxin was injected into the masseter and temporalis; great improvement in trismus and bruxism was noted after 3 weeks. One further treatment improved the mouth opening on the following week and the patient was discharged from our care to be reviewed when required. PMID:17123443

  16. Objective tinnitus from palatal myoclonus. Use of botulinum toxin: a case report.

    Science.gov (United States)

    Conill Tobías, Noemi; de Paula Vernetta, Carlos; García Callejo, Francisco Javier; Marco Algarra, Jaime

    2012-01-01

    Objective tinnitus can have many different etiologies, palatal myoclonus being one of the less frequent. This type of tinnitus is generated by involuntary rhythmic contraction of the soft palate, which generates an audible click for the patient and for the explorer. Botulinum toxin achieves temporary muscle paralysis through presynaptic inhibition of the acetylcholine level at the neuromuscular union. We present a patient with long-term objective tinnitus, along with this patient's response to botulinum toxin injection.

  17. Botulinum Neurotoxin Serotype F: Identification of Substrate Recognition Requirements and Development of Inhibitors with Low Nanomolar Affinity

    Science.gov (United States)

    2007-11-02

    toxin, secreted by Clostridium tetani , and the seven serologically distinct botulinum toxins, designated types A-G, produced by various strains of... Clostridium botulinum, Clostridium baratii, and Clostridium butyricum (1-3). They are the most toxic substances known (4). Each neurotoxin is synthesized as...The latter characteristic distinguishes BoNT F from other zinc metalloendoproteases, including BoNTs A and B. 15. SUBJECT TERMS Clostridium botulinuim

  18. Dataset of botulinum toxin A influence on interleukins under neuropathy.

    Science.gov (United States)

    Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara; Przewlocka, Barbara; Mika, Joanna

    2016-12-01

    Our data show that botulinum toxin A (BoNT/A) didn't influence motor functions in naïve and CCI-exposed rats, but diminished the neuropathic pain-related behavior. The results indicate that BoNT/A administration diminished the spinal Iba-1 positive cells activation and, in parallel, downregulated IL-1beta. Moreover, we observed that in DRG the protein level of pronociceptive factors (IL-1beta and IL-18) decreased and antinociceptive (IL-10 and IL-1RA) factors increased. Additionally, our behavioral analysis shows that chronic minocycline treatment together with a single BoNT/A injection in CCI-exposed rats has beneficial analgesic effects (M. Zychowska, E. Rojewska, W. Makuch, S. Luvisetto, F. Pavone, S. Marinelli, B. Przewlocka, J. Mika, 2016) [1].

  19. Dataset of botulinum toxin A influence on interleukins under neuropathy

    Directory of Open Access Journals (Sweden)

    Magdalena Zychowska

    2016-12-01

    Full Text Available Our data show that botulinum toxin A (BoNT/A didn’t influence motor functions in naïve and CCI-exposed rats, but diminished the neuropathic pain-related behavior. The results indicate that BoNT/A administration diminished the spinal Iba-1 positive cells activation and, in parallel, downregulated IL-1beta. Moreover, we observed that in DRG the protein level of pronociceptive factors (IL-1beta and IL-18 decreased and antinociceptive (IL-10 and IL-1RA factors increased. Additionally, our behavioral analysis shows that chronic minocycline treatment together with a single BoNT/A injection in CCI-exposed rats has beneficial analgesic effects (M. Zychowska, E. Rojewska, W. Makuch, S. Luvisetto, F. Pavone, S. Marinelli, B. Przewlocka, J. Mika, 2016 [1].

  20. Botulinum toxin treatment for limb spasticity in childhood cerebral palsy

    Directory of Open Access Journals (Sweden)

    Vito ePavone

    2016-02-01

    Full Text Available CP is the most common cause of chronic disability in childhood occurring in 2 to 2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects and possible resistance as well as specific use in the upper and lower limbs muscles

  1. Botulinum Toxin Treatment for Limb Spasticity in Childhood Cerebral Palsy

    Science.gov (United States)

    Pavone, Vito; Testa, Gianluca; Restivo, Domenico A.; Cannavò, Luca; Condorelli, Giuseppe; Portinaro, Nicola M.; Sessa, Giuseppe

    2016-01-01

    CP is the most common cause of chronic disability in childhood occurring in 2–2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX) has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects, and possible resistance as well as specific use in the upper and lower limbs muscles. PMID:26924985

  2. The use of botulinum toxin as primary or adjunctive treatment for post acne and traumatic scarring

    Directory of Open Access Journals (Sweden)

    Greg J Goodman

    2010-01-01

    Full Text Available Background : Botulinum toxin has been utilised successfully in many facial and extra facial regions to limit superfluous movement. Scars, whether traumatic or disease-related, are treated with many modalities. Objective: To assess the available literature concerning the prophylactic use of botulinum toxin for the improvement in the cosmetic outcome of scars induced by surgery and to examine its role in the treatment of established scars alone, as also combined with other modalities. Material and Methods : The results of the prophylactic use of botulinum toxin to limit the resultant scarring from surgery are examined by a literature review. The primary and adjunctive use of botulinum toxin in the treatment of post acne and post surgical and traumatic scars is explored by case examples. Results : Literature review and personal experience shows good Improvement in the appearance of scars with the use of botulinum toxin alone or with other adjuvant modalities in the treatment of scars. Conclusion : Botulinum toxin would appear to be useful both in the prophylaxis and treatment of certain types of scars.

  3. Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats

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    Panunzi Simona

    2003-09-01

    Full Text Available Abstract Background Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions. The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl. Methods Sixty-four rats were randomized in two groups and laparotomized. One group was treated with botulinum toxin-A 10 U by multiple submucosal gastric injections, while the second group was injected with saline. Two weeks later, acid secretion was stimulated by pyloric ligation and acid output was measured. Body weight, food and water intake were also recorded daily. Results HCl production after pyloric ligation was found to be significantly lower in botulinum toxin-treated rats (657 ± 90.25 micromol HCl vs. 1247 ± 152. P = 0.0017. Botulinum toxin-treated rats also showed significantly lower food intake and weight gain. Conclusions Botulinum toxin type A reduces stimulated gastric acidity. This is likely due either to inhibition of the cholinergic stimulation of gastric parietal cells, or to an action on the myenteric nervous plexuses. Reduction of growth and food intake may reflect both impaired digestion and decreased gastric motility.

  4. Local injection of botulinum toxin A: an alternative therapy for axillary osmidrosis.

    Science.gov (United States)

    Xie, Aiguo; Nie, Lanjun; Tan, Qian

    2014-02-01

    The objective of this study was to investigate the efficacy of local injection of botulinum toxin A for treating axillary osmidrosis. One hundred and fifty patients with axillary osmidrosis were randomly divided to receive botulinum toxin A injection treatment (50 U of botulinum toxin A was injected intracutaneously into 6-20 different sites within each axilla, n = 74) or surgical excision of the apocrine glands (n = 76). The patients were followed up for 1-3 months to analyze the therapeutic effect and complications of the two methods. The curative effect in patients with mild and moderate axillary osmidrosis was not significantly different between the botulinum toxin A injection group and operation group. However, for patients with severe axillary osmidrosis, surgery treatment seemed to be superior to botulinum toxin A treatment (P = 0.005). There was also no significant difference in the modified Dermatology Life Quality Index between the two treatments. Two cases showed complications related to hemorrhage and incision infection in the operation group. In conclusion, local injection of botulinum toxin A is a safe, fast and effective treatment for mild and moderate axillary osmidrosis, but the long-term effect remains to be further investigated.

  5. Clinical resistance to three types of botulinum toxin type A in aesthetic medicine.

    Science.gov (United States)

    Stephan, Farid; Habre, Maya; Tomb, Roland

    2014-12-01

    Botulinum toxin injections have become the most frequent noninvasive cosmetic procedure carried out worldwide. Botulinum toxin has also multiple other indications in different medical fields. However, with the repetition of injections, a new concern has emerged: clinical resistance and loss of effectiveness of the treatment. After reporting a case of primary nonresponsiveness to three types of botulinum toxin type A injections, we conducted a review about all factors leading to the primary or secondary nonresponsiveness, as well as the factors affecting the immunogenicity of this neurotoxin. Most of the reports and studies focused on secondary resistance to botulinum toxin (BT) and the neurotoxin immunogenicity; primary nonresponsiveness was rarely reported. Factors leading to primary or secondary resistance to BT injections were numerous. In the majority of the studies, development of neutralizing antibodies to botulinum toxin was considered responsible of the induced clinical resistance. Patients should be aware of this rising concern as well as clinicians who should learn how to minimize the risk of resistance development, sparing the patients more invasive treatment modalities. Further studies related to botulinum toxin resistance are needed.

  6. First report of an infant botulism case due to Clostridium botulinum type Af.

    Science.gov (United States)

    de Jong, Laura I T; Fernández, Rafael A; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R; Dykes, Janet K; Lúquez, Carolina

    2015-02-01

    Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide.

  7. First Report of an Infant Botulism Case Due to Clostridium botulinum Type Af

    Science.gov (United States)

    de Jong, Laura I. T.; Fernández, Rafael A.; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R.; Dykes, Janet K.

    2014-01-01

    Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide. PMID:25502535

  8. The changes of serum proteome and tissular pathology in mouse induced by botulinum toxin E injection.

    Science.gov (United States)

    Wang, J F; Mao, X Y; Zhao, C

    2014-01-01

    The experiment were performed to investigate the poisoning-related proteins and main pathological changes after mouse suffered from injection of botulinum toxin serotype E. Dose of 0.75 LD50 botulinum toxin serotype E per mice were administrated by intraperitoneal injection. Survival mouse were picked as experimental group. The blood were collected from orbital blood and serum sample was separated by centrifugation. The heart, liver, spleen, lung, kidney were fixed in 10 % neutral buffered formalin and then developed paraffin sections. Serum protein components were analyzed by SDS-PAGE gel electrophoresis coupled with 2-DE SDS-PAGE gel electrophoresis. Differentially expressed proteins were analyzed by PDQUest8.0 software and subjected to ion trap mass spectrometry equipped with a high performance liquid chromatography system. The observation of pathological section showed that heart, liver, spleen, lung, kidney exhibited pathological changes in different degree, especially in heart, liver and lung tissues. Heart muscle tissue display serious inflammatory response, heart muscle fiber compulsively expanded and filled with erythrocyte and inflammatory exudates, some heart muscle fiber ruptured, even necrosis; hepatic cell in edge of liver occur apoptosis and some hepatic cell have disintegrated, and even died; pulmonary alveoli broken and partial vein filled with blood. Serum proteins component present a significant changes between control serum and botulism in 24 h by SDS-PAGE gel electrophoresis and 2-DE-SDS-PAGE gel electrophoresis. Twenty differentially expressed protein spots were observed in 2-DE profiles, in which 14 protein spots were undetectable in serum proteome under botulism, 3 protein spots exclusively expressed in state of botulism, 3 protein spots were low-expressed in serum proteome under botulism. Fourteen proteins have been identified among 20 spots elected on two-dimensional electrophoresis gels. Crystal proteins family exclusively expressed in

  9. Distribution of the Toxin following Medial Rectus Muscular Injection of Botulinum Toxin Gel in Rabbits

    Institute of Scientific and Technical Information of China (English)

    Jingchang Chen; Guanghuan Mai; Xinping Yu; Huanyuan Yu; Heping Wu; Xiaoming Lin; Daming Deng; Ying Kang

    2005-01-01

    Purpose: To determine the distribution of the toxin among individual muscles after intramuscular injection of botulinum toxin gel.Methods: One eye of 7 New Zealand white rabbits was randomized into group A, and the contralateral eye was into group B. Eyes in group A received medial rectus intramuscular injection of 2.5 IU of 125I-BTX-A gel in 0.1 ml, and those in group B received equivalent amount of 125I-BTX-A solution by medial rectus intramuscular injection. Four rectus muscles and the levator palpebrae superioris were harvested and the radioactivity of muscles was measured 16 hours after the injection.Results: In group A, the radioactivity of per gram medial rectus was significantly higher than that of other muscles (P < 0.01), and there was no statistically significant difference in the radioactivity of per gram muscles among other muscles (P > 0.05). In group B, the radioactivity of per gram medial rectus and levator palpebrae superioris was significantly higher than that of other muscles respectively(P < 0.05), and the difference in the radioactivity of per gram muscles between medial rectus and levator palpebrae superioris was not statistically significant (P > 0.05). The radioactivity of per gram medial rectus in group A was higher than that in group B (t=3.731 ,P=0.01), and there was no significant difference in the radioactivity of per gram muscles among other homonymous muscles (P > 0.05).Conclusion: The toxin dispersed principally in the injected muscle and the local concentration of the toxin was much high following intramuscular injection of botulinum toxin gel.

  10. Clostridium botulinum Type E Toxins Bind to Caco-2 Cells by a Different Mechanism from That of Type A Toxins

    Directory of Open Access Journals (Sweden)

    Zhang,Kai

    2012-06-01

    Full Text Available Cultured Clostridium botulinum strains produce progenitor toxins designated as 12S, 16S, and 19S toxins. The 12S toxin consists of a neurotoxin (NTX, 7S and a non-toxic non-hemagglutinin (NTNH. The 16S and 19S toxins are formed by conjugation of the 12S toxin with hemagglutinin (HA, and the 19S toxin is a dimer of the 16S toxin. Type A cultures produce all 3 of these progenitor toxins, while type E produces only the 12S toxin. The 7S toxin is cleaved into heavy (H and light (L chains by a protease(s in some strains, and the H chain has 2 domains, the N-terminus (Hn and C-terminus (Hc. It has been reported that type A toxins bind to the intestinal cells or cultured cells via either HA or Hc. In this study, we investigated the binding of type A and E toxins to Caco-2 cells using Western blot analysis. Both the type E 7S and 12S toxins bound to the cells, with the 7S toxin binding more strongly, whereas, in the type A strain, only the 16S/19S toxins showed obvious binding. Pre-incubation of the type E 7S toxin with IgG against recombinant type E Hc significantly inhibited the 7S toxin binding, indicating that Hc might be a main binding domain of the type E toxin.

  11. Reconstituting botulinum toxin drugs: shaking, stirring or what?

    Science.gov (United States)

    Dressler, Dirk; Bigalke, Hans

    2016-05-01

    Most botulinum toxin (BT) drugs are stored as powders which need to be reconstituted with normal saline before clinical use. As botulinum neurotoxin (BNT), the therapeutically active ingredient, is a large double-stranded protein the process of reconstitution should be performed with special attention to mechanical stress applied. We wanted to test the mechanical stability of BNT during the reconstitution process. For this, 100 MU onabotulinumtoxinA (Botox(®), Irvine, CA, USA) was reconstituted with 2.0 ml of NaCl/H2O. Gentle reconstitution (GR) was performed with a 5 ml syringe, a 0.90 × 70 mm injection needle, one cycle of injection-aspiration-injection and two gentle shakes of the vial. Aggressive reconstitution (AR) was performed with a 5 ml syringe, a 0.40 × 40 mm injection needle, ten injection-aspiration-injection cycles and 30 s of continuous shaking of the vial. AR increased the time to paralysis in the mouse hemidiaphragm assay (HDA) from 72.0 ± 4.6 to 106.0 ± 16.0 min (*p = 0.002, two-tailed t test after Kolmogorov-Smirnova test with Lilliefors correction for normal distribution). Construction of a calibration curve revealed that the increase in the time to paralysis was correlated with a loss of potency of from 100 to 58 MU (-42 %). BT users should use large diameter injection needles for reconstitution, apply two or three injection-aspiration-injection cycles and, maybe, shake the vials a few times to rinse the entire glass wall. Aggressive reconstitution with small diameter needles, prolonged injection-aspiration-injection and violent shaking should be avoided.

  12. Botulinum toxin in the treatment of orofacial tardive dyskinesia : A single blind study

    NARCIS (Netherlands)

    Slotema, Christina W.; van Harten, Peter N.; Bruggeman, Richard; Hoek, Hans W.

    2008-01-01

    Objective: Orofacial tardive dyskinesia (OTD) is difficult to treat and Botulinium Toxin A (BTA) may be an option. Methods: In a single blind (raters were blind) study (N= 12, duration 33 weeks) OTD was treated with Botulinum Toxin A in three consecutive sessions with increasing dosages. The severit

  13. Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation

    Science.gov (United States)

    Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

    1984-02-01

    Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

  14. Botulinum toxin for treating muscular temporomandibular disorders: a systematic review

    Directory of Open Access Journals (Sweden)

    Eduardo Machado

    2012-12-01

    Full Text Available OBJECTIVE: This study, through a systematic literature review, aims to analyze the effectiveness of Botulinum Toxin as a treatment for masticatory myofascial pain and muscles temporomandibular disorders (TMD. METHODS: Survey in research bases: MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs and BBO, between the years of 1966 and April 2011, with focus in randomized or quasi-randomized controlled clinical trials, blind or double-blind. RESULTS: After applying the inclusion criteria, 4 articles comprised the final sample: 3 were double-blind randomized controlled clinical trials and 1 was single-blind randomized controlled clinical trial. CONCLUSIONS: According to the literature, there is lack of evidence about the real effectiveness of botulinum toxin in the treatment of masticatory myofascial pain and muscular TMD. Thus, further randomized controlled clinical trials, with representative samples and longer follow-up time, to assess the real effectiveness of the technique are needed.OBJETIVO: este trabalho, por meio de uma revisão sistemática da literatura, teve como objetivo analisar a efetividade da toxina botulínica como tratamento para dor miofascial mastigatória e disfunções temporomandibulares (DTM musculares. MÉTODOS: pesquisa nas bases de dados Medline, Cochrane, Embase, Pubmed, Lilacs e BBO, no período entre 1966 e abril de 2011, com enfoque em estudos clínicos controlados randomizados ou quase-randomizados, cegos ou duplo-cegos. RESULTADOS: após a aplicação dos critérios de inclusão, chegou-se a 4 artigos, sendo que 3 eram estudos clínicos controlados randomizados duplo-cego e 1 era estudo clínico controlado randomizado simples-cego. CONCLUSÕES: pela análise da literatura, verificou-se um número reduzido de evidências significativas sobre a real efetividade da toxina botulínica no tratamento da dor miofascial e de DTM musculares. Assim, são necessários novos estudos clínicos controlados randomizados, com amostras

  15. Poison as cure: a clinical review of botulinum toxin as an invaluable drug

    Directory of Open Access Journals (Sweden)

    J. Bali

    2005-12-01

    Full Text Available Botulinum toxin is the most potent toxin known. It is readily absorbed from mucosal surfaces. If dispersed as an aerosol or mixed in the food or water it can lead to a large outbreak of botulism. The disease presents as a symmetric descending paralysis in an afebrile patient. Cranial nerve involvement with diplopia, dysarthria, dysphonia, dysphagia and respiratory paralysis is seen after a variable incubation period. The treatment is mainly supportive. The source of the toxin is Clostridium botulinum, an anaerobic gram-positive spore-forming organism. Some other species of Clostridium like C. butyricum and C. baratii also produce the toxin. The toxin is heat labile and can be inactivated by heating at 100°C for 10 minutes. The toxin acts at the peripheral cholinergic nerve terminals at the neuromuscular junctions, postganglionic parasympathetic ganglia, etc, and affects neurotransmitter release by inhibiting exocytosis. Clinical uses in various medical fields were found for it.

  16. The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain.

    Science.gov (United States)

    Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

    2016-07-22

    The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.

  17. Validation of a new photogrammetric technique to monitor the treatment effect of Botulinum toxin in synkinesis.

    Science.gov (United States)

    Mabvuure, N T; Hallam, M-J; Venables, V; Nduka, C

    2013-07-01

    To validate a new photogrammetric technique for quantifying eye surface area and using this to quantify the degree of improvement in symmetry in patients with oral-ocular synkinesis following Botulinum toxin injection. Feasibility study and retrospective outcomes analysis Ten patients' photographs were chosen from a photographic database. Their eye surface areas were measured independently by two raters using a graphics tablet. One rater repeated the procedure after 15 days. Bland-Altman plots were computed, ascertaining inter-rater and intra-rater variability. The eye surface areas of 19 patients were then derived from photographs taken before and after Botulinum toxin injections. Paired t-tests were used to analyse the significance of the difference in pre- and post-treatment symmetry. Ninety per cent of eye surface areas derived from the two raters were within a coefficient of variation of 0.1 (95% CI: 0.05-0.15). Similarly, 90% of eye surface areas derived from one rater had a coefficient of variation of 0.08 (95% CI: 0.04-0.12). Botulinum toxin significantly reduced synkinesis resulting from lip puckering, Mona Lisa smiling and Hollywood smiling (P<0.05). We have proposed a clinically valid tool for quantifying the effects of Botulinum toxin treatment for oral-ocular synkinesis. We recommend this method be used to monitor the response of such patients when receiving Botulinum toxin treatment.

  18. Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

    Directory of Open Access Journals (Sweden)

    Michael P Cannito

    2008-03-01

    Full Text Available Michael P Cannito, Joel C Kahane, Lesya ChornaSchool of Audiology and Speech-Language Pathology, The University of Memphis, Memphis, TN, USAAbstract: Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age.Keywords: vocal aging, adductor spasmodic dysphonia, botulinum toxin, voice quality, speech fluency

  19. Unilateral transient mydriasis and ptosis after botulinum toxin injection for a cosmetic procedure

    Directory of Open Access Journals (Sweden)

    Akkaya S

    2015-02-01

    Full Text Available Sezen Akkaya,1 Hatice Kübra Kökcen,1 Tuğba Atakan2 1Fatih Sultan Mehmet Education and Training Hospital, Ophthalmology Clinics, Bostanci, Istanbul, 2Aksaray Hospital, Ophthalmology Clinics, Konya, Turkey Abstract: We report a case of unilateral transient mydriasis and ptosis after botulinum toxin injection applied by a medical doctor for a cosmetic procedure. A 36-year-old nurse was referred to our eye clinic with unilateral mydriasis and ptosis in the right eye 3 days after botulinum toxin injection for a cosmetic procedure. Botulinum toxin was applied to her eye by a doctor at her hospital who was not an ophthalmologist. She was treated with topical apraclonidine 0.5% ophthalmic solution. Her ptosis decreased to 2 mm with apraclonidine and her visual axis improved. Mydriasis was present for 3 weeks and then disappeared. Mild ptosis continued for 3 months, then resolved completely. Patients seeking treatment with botulinum toxin A for cosmetic purposes should be warned about the possibility of ptosis and mydriasis after injection. If these side effects are seen, the patient must be referred to an ophthalmologist for appropriate management. Keywords: botulinum toxin, mydriasis, ptosis

  20. Structures of Clostridium Botulinum Neurotoxin Serotype A Light Chain Complexed with Small-Molecule Inhibitors Highlight Active-Site Flexibility

    Energy Technology Data Exchange (ETDEWEB)

    Silvaggi,N.; Boldt, G.; Hixon, M.; Kennedy, J.; Tzipori, S.; Janda, K.; Allen, K.

    2007-01-01

    The potential for the use of Clostridial neurotoxins as bioweapons makes the development of small-molecule inhibitors of these deadly toxins a top priority. Recently, screening of a random hydroxamate library identified a small-molecule inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (BoNT/A-LC), 4-chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo efficacy in mice and no toxicity. We describe the X-ray crystal structures of BoNT/A-LC in complexes with two potent small-molecule inhibitors. The structures of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic hydroxamate bound are compared to the structure of the enzyme complexed with L-arginine hydroxamate, an inhibitor with modest affinity. Taken together, this suite of structures provides surprising insights into the BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket. Information gained from these structures will inform the design and optimization of more effective small-molecule inhibitors of BoNT/A-LC.

  1. Lower facial remodeling with botulinum toxin type A for the treatment of masseter hypertrophy*

    OpenAIRE

    Klein,Fernanda Homem de Mello de Souza; Brenner,Fabiane Mulinari; Sato,Maurício Shigeru; Robert,Fernanda Manfron Batista Rosas; Helmer, Karin Adriane

    2014-01-01

    BACKGROUND: Masseter hypertrophy has been treated with botulinum toxin injections because of esthetic complaints especially in Asians. OBJECTIVES: The goal of the present study was to evaluate the efficacy of abobotulin toxin use in masseter hipertrophy treatment in Brazilians. METHODS: Ten Brazilian female patients with masseter hypertrophy were subjected to injections of 90U of abobotulinum toxin A applied on each side respecting the safety zone stabilished in literature and were followed u...

  2. In situ detection of the Clostridium botulinum type C1 toxin gene in wetland sediments with a nested PCR assay

    Science.gov (United States)

    Williamson, J.L.; Rocke, T.E.; Aiken, Judd M.

    1999-01-01

    A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.

  3. Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat

    DEFF Research Database (Denmark)

    Pingel, Jessica; Hultborn, Hans; Naslund-Koch, Lui

    2017-01-01

    Botulinum toxin (Btx) is used in children with cerebral palsy and other neurological patients to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in the central gain of the stretch reflex circuitry in response to botulinum toxin injection...

  4. Cervical dystonia : Improved treatment response to botulinum toxin after referral to a tertiary centre and the use of polymyography

    NARCIS (Netherlands)

    Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Standaar, T. S. M.; Postma, Marten; Tijssen, M. A. J.

    2013-01-01

    Rationale: Cervical dystonia is the most common form of (primary) dystonia. The first line of treatment for cervical dystonia is intramuscular injections with botulinum toxin. To optimise the response to botulinum toxin proper muscles selection is required. Pre-treatment polymyographic EMG in additi

  5. Structure- and Substrate- Based Inhibitor Design for Clostridium botulinum Neurotoxin Serotype A*

    Energy Technology Data Exchange (ETDEWEB)

    Kumaran,D.; Rawat, R.; Ludivico, M.; Ahmed, S.; Swaminathan, S.

    2008-01-01

    The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex proteins and block the release of neurotransmitters that cause flaccid paralysis and are considered potential bioweapons. Botulinum neurotoxin type A is the most potent among the clostridial neurotoxins, and to date there is no post-exposure therapeutic intervention available. To develop inhibitors leading to drug design, it is imperative that critical interactions between the enzyme and the substrate near the active site are known. Although enzyme-substrate interactions at exosites away from the active site are mapped in detail for botulinum neurotoxin type A, information about the active site interactions is lacking. Here, we present the crystal structures of botulinum neurotoxin type A catalytic domain in complex with four inhibitory substrate analog tetrapeptides, viz. RRGC, RRGL, RRGI, and RRGM at resolutions of 1.6-1.8 Angstroms . These structures show for the first time the interactions between the substrate and enzyme at the active site and delineate residues important for substrate stabilization and catalytic activity. We show that OH of Tyr366 and NH2 of Arg363 are hydrogen-bonded to carbonyl oxygens of P1 and P1' of the substrate analog and position it for catalytic activity. Most importantly, the nucleophilic water is replaced by the amino group of the N-terminal residue of the tetrapeptide. Furthermore, the S1' site is formed by Phe194, Thr215, Thr220, Asp370, and Arg363. The Ki of the best inhibitory tetrapeptide is 157 nm.

  6. Plantar focal idiopathic hyperhidrosis and botulinum toxin: a pilot study.

    Science.gov (United States)

    Campanati, Anna; Bernardini, Maria Luisa; Gesuita, Rosaria; Offidani, Annamaria

    2007-01-01

    Botulinum toxin is a safe and effective treatment for idiopatic focal axillary and palmar hyperhidrosis, but very few data are reported in the literature on its effect on plantar idiopatic hyperhidrosis. The current study was undertaken to investigate the impact of BTX-A administration on sweat production and quality of life in patients suffering from plantar hyperhidrosis. Ten patients with idiopathic, recalcitrant plantar hyperhidrosis were included in a pilot study and underwent intradermal injections with 100 MU of BTX-A in the plantar skin, bilaterally. All the patients were followed for 16 weeks after treatment with objective (Minor's test) and subjective (DLQI test) evaluation. Patients experienced an improvement of symptoms with a significant decrease of Minor's test and DLQI levels for 12 weeks. No significant side effects occurred in any treated patient. BTX-A seems to be a promising treatment for plantar hyperhidrosis. However, clinical trials on larger patient series are needed in order to evaluate its safety and effectiveness for this application.

  7. Botulinum toxin treatment for slipping rib syndrome: a case report.

    Science.gov (United States)

    Pirali, Caterina; Santus, Gianna; Faletti, Sofia; De Grandis, Domenico

    2013-10-01

    Slipping rib syndrome (SRS) is a musculoskeletal cause of severe and recurrent thoracic or abdominal pain. The etiology of SRS is unknown, it seems to arise from costal hypermobility with a tendency of one of the ribs (usually from 8th to 10th but also 11th and 12th have been described) to slip under the superior adjacent rib. Its prevalence is underestimated because SRS is mainly a clinical diagnosis, frequently missed. The critical aspect of the diagnosis is knowledge of the condition itself, which, when lacking, often results in the patient being referred to many different specialists and exposed to unnecessary and costly investigations. The management of the condition includes conservative techniques such as manipulation, localized anesthetic, and steroid or anesthetic nerve block. However, where conservative therapy fails, surgical treatment, with excision of the rib, may be performed. In this paper we describe the case of a patient with persistent and debilitating flank pain who, after many investigations, was diagnosed with SRS. The usual conservative treatment failed, after which we treated the patient with injections of incobotulinumtoxin A into muscles inserting on the inferior side of the rib cage (quadratus lumborum muscle, muscle transversus abdomini, abdominal external oblique muscle, and recto abdomini) achieving a complete relief from pain. To our knowledge botulinum toxin has never been proposed before for the treatment of SRS. We believe that it should be considered as a therapeutic option, especially where other medical treatments have failed or as an intermediate step before surgical intervention.

  8. Treatment diary for botulinum toxin spasticity treatment: a pilot study.

    Science.gov (United States)

    Biering-Sørensen, Bo; Iversen, Helle K; Frederiksen, Inge M S; Vilhelmsen, Jeanet R; Biering-Sørensen, Fin

    2017-02-20

    The aim of this study is to develop a treatment diary for patients receiving spasticity treatment including botulinum toxin injection and physiotherapy and/or occupational therapy. The diary focuses on problems triggered by skeletal muscle overactivity; agreed goals for treatment and the patient's self-evaluation of achievement on the Goal Attainment Scale; which skeletal muscles were injected; physiotherapists' and occupational therapists' evaluation of the patients' achievement of objectives on the Goal Attainment Scale; and proposals for optimization of treatment and changing goals. The evaluation included a satisfaction questionnaire and the WHO-QoL BREF and WHO-5 well-being score. Overall, 10 patients were enrolled in the pilot study. The patients were generally satisfied with the diary, found that it involved them more in their treatment and made it easier to set personal goals, and found it worth the time spent using it. However, no clear advantage in relation to their quality of life (WHO-QoL BREF and WHO-5 well-being score) was reported.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

  9. Botulinum toxin A inhibits salivary secretion of rabbit submandibular gland

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Shan; Hui Xu; Zhi-Gang Cai; Li-Ling Wu; Guang-Yan Yu

    2013-01-01

    Botulinum toxin A (BTXA) has been used in several clinical trials to treat excessive glandular secretion;however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor (M3 receptor) and aquaporin-5 (AQP5) mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular glands.

  10. Remote Effects of Local Injection of Botulinum Toxin Type A

    Institute of Scientific and Technical Information of China (English)

    Wan Xinhua; Tang Xiaofu; Cui Liying

    2000-01-01

    Objective To assess the seventy and temporal profile of remote effects of botulinum toin type A, BTX-A (Botox from Allergan Inc.,USA and CBTX-A made by Lanzhou Biological Products Institute, China ) injected locally on neuromuscular transmission. Background Recently the local injection of BTX-A has been accepted as a breakthrough in the treatment of a variety of spasmodic disorders, and remote effects of BTX-A on the neuromuscular transmission are concemed. Methods Fourty patients who had enrolled in a prospective open study with Botox or CBTX-A for their movement disorders were studied, 18 cases with Botox and 22 cases with CBTX-A. SFEMG in the extensor digitorum communis muscle or tibialis anterior muscle was performed before and 2-3weeks, 5-8weeks, 4-5 months after injection of Botox or CBTX-A, totally 119 times. Results The significant increase of jitter was demonstrated 2-3weeks after injections in both groups and MCD was in direct proportion to dose of injections.Fiber density value increased at the same time or later and still existed until 4-5 months after injections. Conclusion There are subclinical effects on neuromuscular transmission of remote uninjected muscles after injections of Botox and CBTX A, which indicates that the toxin spread remotely from the site of injection.

  11. Treatment of Raynaud's phenomenon with botulinum toxin type A.

    Science.gov (United States)

    Zhang, Xiaolong; Hu, Yong; Nie, Zhiyu; Song, Ye; Pan, Yougui; Liu, Ying; Jin, Lingjing

    2015-07-01

    Raynaud's phenomenon (RP), an episodic vasospasm of the peripheral arteries, is quite common in general population. The current therapies of RP are limited by efficacy, side effects, and polypharmacy concerns. Botulinum toxin type A (BTX-A) local injections have been reported for the treatment of RP, but the injection sites, concentration and dose of BTX-A were different from each other in previous trials. In addition, so far, there have been no reports concerning local injection of BTX-A in Asian RP patients. Ten patients with RP in China were included in this retrospective study. All the patients had intractable pain and were non-responsive to conservative and/or medical therapy. A patterned BTX-A injection was performed in RP patients, guided by ultrasonography. BTX-A was injected as 20 u/ml devoid of preservatives. Outcomes were measured by ultrasonography, surface temperature, visual analog scale (VAS) for clinical symptoms (pain, numbness, stiffness and swelling), and changes in ulcers or gangrene. Overall, a great improvement in artery flow velocity (P < 0.01), surface temperature (P < 0.01), ulcer and VAS for clinical symptoms, was observed after BTX-A local injection. Complications were very rarely found, and no patients complained of hand weakness and bruise. BTX-A patterned injection guided by ultrasonography might be a useful therapeutic tool in the management of intractable RP.

  12. Improvement of chronic facial pain and facial dyskinesia with the help of botulinum toxin application

    Directory of Open Access Journals (Sweden)

    Ellies Maik

    2007-08-01

    Full Text Available Abstract Background Facial pain syndromes can be very heterogeneous and need individual diagnosis and treatment. This report describes an interesting case of facial pain associated with eczema and an isolated dyskinesia of the lower facial muscles following dental surgery. Different aspects of the pain, spasms and the eczema will be discussed. Case presentation In this patient, persistent intense pain arose in the lower part of her face following a dental operation. The patient also exhibited dyskinesia of her caudal mimic musculature that was triggered by specific movements. Several attempts at therapy had been unsuccessful. We performed local injections of botulinum toxin type A (BTX-A into the affected region of the patient's face. Pain relief was immediate following each set of botulinum toxin injections. The follow up time amounts 62 weeks. Conclusion Botulinum toxin type A (BTX-A can be a safe and effective therapy for certain forms of facial pain syndromes.

  13. Botulinum toxin in the management of sialorrhoea in acquired brain injury

    LENUS (Irish Health Repository)

    Carroll, A

    2016-06-01

    Sialorrhoea as a consequence of severe acquired brain injury can significantly negatively impact on quality of life. Medications used in its management have many side effects which can cause problems in the severely disabled. Botulinum toxin is an effective treatment of sialorrhoea in a number of neurological conditions but may also have a role to play in the management of sialorrhoea following severe ABI. We report on 4 cases of sialorrhoea following acquired brain injury causing a variety of problems, whose parotid glands were injected with Botulinum toxin type A (Dysport) 50mu each, under ultrasound guidance. All cases had a clinically and statistically significant reduction in drooling as measured by the teacher drooling scale (p=0.005) and carers Visual Analogue Scale (p=0.012). There were no side effects reported. Botulinum toxin is an effective treatment for sialorrhoea associated with acquired brain injury.

  14. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value.

    Science.gov (United States)

    Zoons, E; Dijkgraaf, M G W; Dijk, J M; van Schaik, I N; Tijssen, M A

    2012-12-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharmaco-therapeutic and pharmaco-economic value of botulinum toxin as treatment for focal dystonia, which yielded the following results. Botulinum toxin is the most effective treatment for reducing dystonic symptoms measured with dystonia-specific and general questionnaires, and pain in patients with focal dystonia. Seventy-one percent of patients with cervical dystonia had a reduction in neck pain compared to 12 % in placebo groups. Adverse events occur in 58 % of patients during treatment with botulinum toxin compared to 46 % treated with placebo. Especially dry mouth, neck weakness, dysphagia, and voice changes are common. Adverse events are usually mild and self-limiting. Health-related quality of life, measured with the SF-36 is 20-50 points lower in patients with focal dystonia compared to controls and the effect of botulinum toxin on health-related quality of life is unclear. Botulinum toxin treatment is expensive because the drug itself is expensive. Yearly costs for treating a patient with focal dystonia with botulinum toxin range from EUR 347 to EUR 3,633 and the gain in QALYs with BTX treatment is small. Focal dystonia impairs the productivity and the ability to work. At start of botulinum toxin treatment only 47-50 % was working. Botulinum toxin partly improves this. Overall, we conclude that botulinum toxin is an expensive drug with good effects. From a societal perspective, the costs may well weigh up to the regained quality of life. However, the available literature concerning costs, health-related quality of life and labor participation is very limited. An extensive cost-effectiveness study should be performed incorporating all these aspects.

  15. Arrangement of the Clostridium baratii F7 toxin gene cluster with identification of a σ factor that recognizes the botulinum toxin gene cluster promoters.

    Science.gov (United States)

    Dover, Nir; Barash, Jason R; Burke, Julianne N; Hill, Karen K; Detter, John C; Arnon, Stephen S

    2014-01-01

    Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bont gene that is part of a toxin gene cluster that includes several accessory genes. We sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. This TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.

  16. The Efficacy of Botulinum Toxin A Intramuscular Injections in After-Stroke Spasticity

    Directory of Open Access Journals (Sweden)

    Melek Karaçam

    2010-09-01

    Full Text Available OBJECTIVE: Spasticity is a common dysfunction in stroke patients. It hinders the performance of everyday living activities and lowers the quality of life. In this study, it was aimed to investigate the effects of botulinum toxin A therapy on various aspects, such as muscle tone, pain, daily living activities and disability. METHODS: Fifteen patients with stroke presenting with focal spasticity in the botulinum toxin outpatient unit were evaluated. Results before and after treatment were evaluated by applying different scales. Modified Ashworth Scale was applied for the severity of spasticity. The Medical Council Research Scale was used to test muscle power, and the disability scoring scale, Visual Analogue Pain Scale and Barthel index were the other measures tested. RESULTS: It was found that therapy with botulinum toxin A was effective in spasticity. The increased muscle tone and the disability scores decreased prominently after the treatment (p< 0.05. Lower values in pain scores (p< 0.05 also contributed to better functional outcome (p< 0.01. Along with the significantly good outcome according to the scales, the higher scores in quality of life, feeling of well-being, good performance during the physiotherapy sessions, and less medications needed for spasticity were also indications in commencing the therapy of botulinum toxin A in spasticity. CONCLUSION: Spasticity is a complicated condition causing serious disability. Botulinum toxin A is a preferred therapy when there is an increased motor activity. The effects of the agent are reversible and reliable. The duration of the treatment is long-lasting. Since botulinum toxin A is easily applied and the outcome in focal spasticity is favorable, it is recommended as the first-line choice in the treatment of focal spasticity.

  17. Bruxism secondary to brain injury treated with Botulinum toxin-A: a case report

    Directory of Open Access Journals (Sweden)

    Swinson Brian

    2006-11-01

    Full Text Available Abstract We report a successful treatment of bruxism in a patient with anoxic brain injury using botulinum toxin-A (BTX-A. On examination the mouth opening was 0 mm, no feeding was possible through the mouth. Botulinum toxin was injected into the masseter and temporalis; great improvement in trismus and bruxism was noted after 3 weeks. One further treatment improved the mouth opening on the following week and the patient was discharged from our care to be reviewed when required.

  18. Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Kroken, Abby R.; Karalewitz, Andrew P.-A.; Fu, Zhuji; Kim, Jung-Ja P.; Barbieri, Joseph T. (MCW)

    2012-02-07

    Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. Although several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle-associated protein), the entry pathway of BoNT/D is less well understood. Although BoNT/D entry is ganglioside-dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing a ganglioside binding loop (GBL, residues Tyr-1235-Ala-1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe-1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp-1238, located near the N terminus of the ganglioside binding loop, was mostly solvent-inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2. Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies.

  19. [Botulinum toxin for the treatment of pain syndromes].

    Science.gov (United States)

    Ferreira, Joaquim J; Couto, Marina; Costa, João; Coelho, Miguel; Rosa, Mário M; Sampaio, Cristina

    2006-01-01

    Although botulinum toxin (BoNT) is being used for therapeutic purposes for more than 20 years, the list of potential new indications continues to increase and includes various pain syndromes. The pain relief experienced by patients with dystonia and spasticity from intramuscular BoNT injections suggested that other chronic skeletal-muscles pain conditions may also benefit. BoNT inhibits the release of acetylcholine at the neuromuscular junction thereby reducing striatal muscle contractions and the proposed analgesic property was initially attributed to muscular relaxation. A specific analgesic BoNT effect is difficult to conclude from studies where pain is conditioned by other associated symptoms like dystonia, muscle contraction or spasticity. One alternative is to critically appraise clinical trials where BoNT was studied as the active intervention and pain evaluated as an outcome. From this analysis there is convincing evidence for the effectiveness of BoNT in the treatment of pain associated with cervical dystonia. For all other pain syndromes there have been relatively few, small sized, placebo-controlled studies (myofascial pain syndrome, chronic neck and low back pain, piriformis syndrome and fibromyalgia) and the results of these studies have been contradictory or non conclusive. To establish the analgesic properties of BoNT there is a need for appropriately designed, exploratory randomized controlled studies in well accepted human models of nociceptive or neuropathic pain. This does not exclude the subsequent need to conduct pragmatic trials to evaluate the effectiveness of BoNT in conditions where the improvement of pain or any associated clinical sign or symptom may be of clinical relevance.

  20. Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows

    Science.gov (United States)

    Moeller, R.B.; Puschner, B.; Walker, R.L.; Rocke, T.E.; Smith, S.R.; Cullor, J.S.; Ardans, A.A.

    2009-01-01

    Three adult lactating Holstein cows were injected in the subcutaneous abdominal vein with 175 ng/kg of body weight of Clostridium botulinum type C toxin (451 cow median toxic doses) to determine if this botulinum toxin crosses the blood-milk barrier. Whole blood (in sodium heparin) and clotted blood serum samples were taken at 0 min, 10 min, and 3, 6, 9, and 12 h postinoculation. Milk samples were taken at 0 min and at 3, 6, 9 and 12 h postinoculation. All samples were tested for the presence of the toxin using the mouse bioassay and immunostick ELISA test. The immunostick ELISA identified the toxin in whole blood and the mouse bioassay identified the toxin in serum at all times examined in all 3 animals. Toxin was not identified by either detection method in milk samples collected from the 3 animals. From these results, it appears that Clostridium botulinum type C toxin does not cross from the blood to the milk in detectable concentrations. ?? American Dairy Science Association, 2009.

  1. Endocardial botulinum toxin injection into ganglionated plexi in order to reduce atrial fibrillation inducibility

    Directory of Open Access Journals (Sweden)

    А. Г. Стрельников

    2016-01-01

    Full Text Available Objective. Prior animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress atrial fibrillation (AF inducibility. The purpose of the present study was to assess the efficacy and safety of endocardial botulinum toxin injection into epicardial fat pads and intramyocardial left atrial ganglionated plexi (GP for preventing AF.Methods. Twenty-four dogs were separated into 3 groups: endocardial approach for botulinum toxin (Xeomin, Germany injection into epicardial fat pads and intramyocardial GPs; endocardial approach for placebo injection (0.9% normal saline; control 1; n = 8 and epicardial approach for botulinum toxin injection (control 2; n = 8.Results. A mean of 6.9±1.7 intramyocardial injections (10 U/0.2 mL at each and 3 injections (50 U/1 mL at each were administered into each site exhibiting a positive vagal response and into each epicardial fat pad in all groups (p>0.05 between groups.The injections of botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions. This effect correlated with less pronounced ERP shortening in response to vagal nerve stimulation. Suppression of AF inducibility was observed at 7 days after endocardial botulinum toxin injections. The level of AF inducibility was: at 7 days – 57% (p<0.001 vs placebo; p<0.001 vs baseline; at 14 days – 61% (p<0.001 vs placebo; p<0.001 vs baseline; at 1 month – 38% (p<0.001 vs placebo; p<0.001 vs baseline; at 3 months – 23% (p = 0.003; p = 0.06 vs baseline. There were no differences between botulinum groups (p>0.05 for all. The effect of AF suppression disappeared at 3 months. No procedure-related complications occurred.Conclusion. Botulinum toxin injection into intramyocardial GPs and epicardial fat pads by an endocardial approach is feasible and safe. It provides complete removal of cardiac vagal responses and reliably reduces vulnerability to atrial fibrillation.

  2. Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

    Science.gov (United States)

    Hassel, Bjørnar

    2013-01-01

    Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection. PMID:23299659

  3. Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

    Directory of Open Access Journals (Sweden)

    Bjørnar Hassel

    2013-01-01

    Full Text Available Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection.

  4. Economics of botulinum toxin therapy: influence of the abobotulinumtoxinA package size on the costs of botulinum toxin therapy.

    Science.gov (United States)

    Dressler, Dirk; Adib Saberi, Fereshte

    2017-01-01

    AbobotulinumtoxinA (Dysport®) was distributed for many years in vials containing 500MU (D500). Recently a new 300MU vial (D300) was additionally introduced (introduction). We wanted to explore whether more differentiated package sizes allow for more economic use of Dysport® in a large neurological botulinum toxin (BT) outpatient clinic. The study followed a retrospective chart review design based on our digital BT therapy data bank. All patients receiving Dysport® exclusively in a constant dose during the observation period (introduction ± 7 months) were included. Economic calculations are based on Dysport® prices as officially advertised in Germany. Sharing of vials between patients was not allowed. Altogether 83 patients (51 with dystonia, 25 with spasticity, 3 with hemifacial spasm, 4 with other diagnoses) were included in this study. The total amount of BT used before and after introduction was 102525MU, the amount prescribed 138000MU and 116300MU (-21700MU, -15.7%), the costs €146103 and €125250 (-€ 20853, -14.3%). The price for D500 before and after introduction was €529.36, for D300 €339.71. The D500 price for 1MU before and after introduction is €1.0587, the D300 price for 1MU €1.1324 (+ €0.073, +7.0% against D500). More flexible packaging reduces drug costs for BT therapy considerably. Introducing smaller packaging sizes is technically possible and should be encouraged. Extra costs for registration and logistics are moderate. Further cost reductions may be possible by introduction of even smaller packaging sizes. They can be calculated based on our model.

  5. Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency

    DEFF Research Database (Denmark)

    Saunte, Jon Peiter; Holmes, Jonathan M

    2014-01-01

    .008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p=0...

  6. Age-related botulinum toxin effects on muscle fiber conduction velocity in non-injected muscles

    NARCIS (Netherlands)

    Lange, Fiete; van Weerden, Tiemen W.; van der Hoeven, Johannes H.

    2007-01-01

    Objective: We studied systemic effects of botulinum toxin (BTX) treatment on muscle fiber conduction velocity (MFCV) and possible effects of age. Methods: MFCV was determined by an invasive EMG method in the biceps brachii muscle. Seventeen BTX treated patients and 58 controls were investigated. BTX

  7. Cellular uptake of Clostridium botulinum C2 toxin requires oligomerization and acidification

    NARCIS (Netherlands)

    Barth, H; Blocker, D; Behlke, J; Bergsma-Schutter, W; Brisson, A; Benz, R; Aktories, K

    2000-01-01

    The actin-ADP-ribosylating binary Clostridium botulinum C2 toxin consists of two individual proteins, the binding/translocation component C2II and the enzyme component C2I. To elicit its cytotoxic action, C2II binds to a receptor on the cell surface and mediates cell entry of C2I via receptor-mediat

  8. Effect of multilevel botulinum toxin A and comprehensive rehabilitation on gait in cerebral palsy

    NARCIS (Netherlands)

    Scholtes, Vanessa A.; Dallmeijer, Annet J.; Knol, Dirk L.; Speth, Lucianne A.; Maathuis, Carel G.; Jongerius, Peter H.; Becher, Jules G.

    2007-01-01

    To evaluate the effect of multilevel botulinum toxin A and comprehensive rehabilitation on gait pattern, muscle length, and spasticity, a multicenter randomized trial was performed in 46 children with spastic cerebral palsy who walk with flexed knees. Their mean age was 8.0 years (range 4 to 11 year

  9. Dynamic cortical gray matter volume changes after botulinum toxin in cervical dystonia

    NARCIS (Netherlands)

    Delnooz, C.C.S.; Pasman, J.W.; Warrenburg, B.P.C. van de

    2015-01-01

    Previous electrophysiological and functional imaging studies in focal dystonia have reported on cerebral reorganization after botulinum toxin (BoNT) injections. With the exception of microstructural changes, alterations in gray matter volume after BoNT have not been explored. In this study, we

  10. Efficacy and duration of botulinum toxin treatment for drooling in 131 children.

    NARCIS (Netherlands)

    Scheffer, A.R.T.; Erasmus, C.E.; Hulst, K. van; Limbeek, J. van; Jongerius, P.H.; Hoogen, F.J.A. van den

    2010-01-01

    OBJECTIVE: To address the efficacy of botulinum toxin and the duration of its effect when used on a large scale for the treatment of drooling in children with neurological disorders. DESIGN: Prospective cohort study. SETTING: Academic multidisciplinary drooling clinic. PATIENTS: A total of 131 child

  11. Effect of a clown's presence at botulinum toxin injections in children: a randomized, prospective study

    DEFF Research Database (Denmark)

    Hansen, Lars Kjaersgaard; Kibaek, Maria; Martinussen, Torben;

    2011-01-01

    The effect of the presence of a hospital clown during pediatric procedures has rarely been evaluated. In a pediatric ward, botulinum toxin injection is a painful procedure and a stressful experience for the child. We undertook a study of the effect of the presence of a hospital clown on children...

  12. Cellular uptake of Clostridium botulinum C2 toxin requires oligomerization and acidification

    NARCIS (Netherlands)

    Barth, H; Blocker, D; Behlke, J; Bergsma-Schutter, W; Brisson, A; Benz, R; Aktories, K

    2000-01-01

    The actin-ADP-ribosylating binary Clostridium botulinum C2 toxin consists of two individual proteins, the binding/translocation component C2II and the enzyme component C2I. To elicit its cytotoxic action, C2II binds to a receptor on the cell surface and mediates cell entry of C2I via receptor-mediat

  13. Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Jensen, Bente Rona; Nielsen, Lone M

    2012-01-01

    Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). Methods: Fourteen children with CP performed supervised...

  14. Botulinum toxin versus trihexyphenidyl in cervical dystoni - A prospective, randomized, double-blind controlled trial

    NARCIS (Netherlands)

    Brans, JWM; Lindeboom, R; Snoek, JW; Zwarts, MJ; vanWeerden, TW; Brunt, ERP; vanHilten, JJ; vanderKamp, W; Prins, MH; Speelman, J.D.

    1996-01-01

    Background: Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study. Methods: This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomize

  15. European consensus table on the use of botulinum toxin type A in adult spasticity.

    NARCIS (Netherlands)

    Wissel, J.; Ward, A.B.; Erztgaard, P.; Bensmail, D.; Hecht, M.J.; Lejeune, T.M.; Schnider, P.; Altavista, M.C.; Cavazza, S.; Deltombe, T.; Duarte, E.; Geurts, A.C.H.; Gracies, J.M.; Haboubi, N.H.; Juan, F.J.; Kasch, H.; Katterer, C.; Kirazli, Y.; Manganotti, P.; Parman, Y.; Paternostro-Sluga, T.; Petropoulou, K.; Prempeh, R.; Rousseaux, M.; Slawek, J.; Tieranta, N.

    2009-01-01

    A group of clinicians from across Europe experienced in the use of botulinum toxin type A for the treatment of spasticity following acquired brain injury gathered to develop a consensus statement on best practice in managing adults with spasticity. This consensus table summarizes the current publish

  16. Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin

    DEFF Research Database (Denmark)

    Gazerani, Parisa; Pedersen, N. S.; Drewes, Asbjørn Mohr

    2009-01-01

    BACKGROUND: Clinical evidence has revealed the antipruritic effect of botulinum toxin type A (BoNT/A). BoNT/A is believed to be effective against itch as it inhibits the release of acetylcholine as well as some other substances that may be involved in itch. OBJECTIVES: To investigate the effect...

  17. The use of botulinum toxin type A in cosmetic facial procedures

    NARCIS (Netherlands)

    Jaspers, G. W. C.; Pijpe, J.; Jansma, J.

    2011-01-01

    Over the past decade, facial cosmetic procedures have become more commonplace ill dentistry and oral and maxillofacial surgery. An increasing number of patients seek minimal invasive procedures. One of the most requested procedures is treatment with botulinum toxin type A (BoNTA). Treatment of dynam

  18. Detection of botulinum toxin types A, B, E, and F activity using the quail embryo

    Science.gov (United States)

    We recently demonstrated an effective new model for the detection of botulinum toxin type A using quail embryos in place of the mouse model. These experiments demonstrated that the Japanese quail embryo at 15 days of incubation was an effective vertebrate animal model to detect the activity of botu...

  19. Thickened Saliva after Effective Management of Drooling with Botulinum Toxin A

    Science.gov (United States)

    Erasmus, Corrie E.; van Hulst, Karen; van den Hoogen, Frank J. A.; van Limbeek, Jacques; Roeleveld, Nel; Veerman, Enno C. I.; Rotteveel, Jan J.; Jongerius, Peter H.

    2010-01-01

    Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function…

  20. Thickened Saliva after Effective Management of Drooling with Botulinum Toxin A

    Science.gov (United States)

    Erasmus, Corrie E.; van Hulst, Karen; van den Hoogen, Frank J. A.; van Limbeek, Jacques; Roeleveld, Nel; Veerman, Enno C. I.; Rotteveel, Jan J.; Jongerius, Peter H.

    2010-01-01

    Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function…

  1. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.

    Science.gov (United States)

    Pavlik, Benjamin J; Hruska, Elizabeth J; Van Cott, Kevin E; Blum, Paul H

    2016-03-30

    Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by flow cytometry and found to be dependent on artificial enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by confocal microscopy showed a dissociation of payloads from the early endosome indicating translocation of the chimeric toxin. The natural Clostridium botulinum C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa cells. In the presence of the fusion protein, native cytosolic enzymatic activity of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology.

  2. Botulinum Toxin-A Therapy in Pediatric Urology: Indications for the Neurogenic and Non-Neurogenic Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Lori Dyer

    2009-01-01

    Full Text Available Although, the role of Botulinum Toxin-A in the treatment of the neurogenic and non-neurogenic neurogenic bladder is becoming more defined, this is the first review article to characterize the emerging role of Botulinum Toxin-A in the pediatric urologic population. Injection of Botulinum Toxin-A at the level of the bladder works by inhibiting uninhibited bladder contractions and, possibly, by blocking some of the sensory nerve fibers. In children with sphincter dyssynergy, injection at the level of the urethral sphincter works by inhibiting the involuntary guarding reflex and blocking dyssynergic voiding.

  3. Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.

    Science.gov (United States)

    Suwan-apichon, Olan; Rizen, Michael; Rangsin, Ram; Herretes, Samantha; Reyes, Johann M G; Lekhanont, Kaevalin; Chuck, Roy S

    2006-01-01

    To develop a mouse model of human chronic dry eye (keratoconjunctivitis sicca [KCS]). Under direct visualization with an operating microscope, CBA/J mice received a transconjunctival injection of saline or 1.25, 5, or 20 milliunits (mU) of botulinum toxin B (BTX-B) into the lacrimal gland. The mice were either left unstressed or were subjected to an air blower for 5 h/d, 5 d/wk in fixed temperature and humidity conditions. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at several time points after. Tear production was measured with phenol red-impregnated cotton threads. Corneal fluorescein staining was photographed under cobalt blue light with a digital camera fitted with a macro lens. BTX-B-injected mice displayed significantly decreased tear production until the 4-week time point. Throughout all time points, the addition of environmental blower stress did not appear to alter tear production significantly. Linear regression models, used to evaluate the effects of various doses of BTX-B on tear production, showed that doses higher than 1.25 mU did not provide significantly different outcomes. After 3 days, saline-injected mice showed no corneal staining, whereas BTX-B-injected mice displayed various amounts of staining. At the early time point (day 3), there did not appear to be an additional effect of the blower on corneal fluorescein staining. However, at 1, 2, and 4 weeks, the blower stress appeared to increase the amount of corneal fluorescein staining at each BTX-B dose, although not significantly. Furthermore, at 8 to 10 weeks, in the BTX B-injected groups, corneas had persistent staining, even though tear production had already returned to normal levels. Histopathologic analyses revealed no inflammatory cell infiltration of the stroma or acini of the lacrimal glands and conjunctivae of both saline-injected and BTX-B-injected animals. Intralacrimal gland injection of BTX-B resulted in persistent corneal

  4. Intramuscular distribution of botulinum toxin--visualized by MRI.

    Science.gov (United States)

    Elwischger, K; Kasprian, G; Weber, M; Meyerspeer, M; Linder, C; Auff, E; Prayer, D; Sycha, T; Kranz, G

    2014-09-15

    A precise knowledge of the spread of botulinum toxin (BoNT) in muscle tissue is required to efficiently access endplate zones and increase BoNT's therapeutic efficacy. Here, we aimed to understand the spatiotemporal dynamics of BoNT distribution in skeletal muscle and its modulating factors, such as injected volume and exercise after injection. To visualize distribution in muscle tissue, sagittal, dynamic, balanced fast field echo (BFFE) MRI imaging was performed during injection of 1 ml BoNT/NaCl bolus in spastic biceps brachii muscles (SBB, n=4), and 1 ml NaCl in the right and 2 ml NaCl in the left healthy biceps brachii (HBB, n=6), with or without successive muscle exercise. The pattern of extracellular fluid distribution was evaluated by T2-weighted and diffusion tensor imaging (DTI) sequences. BFFE indicated an immediate increase in hyperintensity, parallel to the muscle fibers, in the shape of a long (5.3±1.7 cm) and thin (0.52±1.3 cm) layer in HBB. The layer in SBB was shorter (3.25±0.6 cm, p=0.01) and tended to be thicker (0.74±2.9 cm, p=0.27). In HBB, an increase in volume (2 ml) resulted in an increase in thickness (0.95±0.2 cm, p=0.015), but a consistent length (5.67±1.3 cm, p=0.54). DTI visualized a change of diffusion, which exceeded the bolus region by approximately 0.5 cm. Redistribution occurred 10 min after injection and was more prominent in HBB, compared to SBB. Additional muscle activity did not alter the diffusion pattern or bolus distribution. Injecting BoNT at different depths perpendicular to the direction of the muscle fiber might optimize the efficacy of BoNT treatment. Additional sites along muscle fibers should be considered in SBB. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Primary hyperhidrosis: Implications on symptoms, daily life, health and alcohol consumption when treated with botulinum toxin.

    Science.gov (United States)

    Shayesteh, Alexander; Boman, Jens; Janlert, Urban; Brulin, Christine; Nylander, Elisabet

    2016-08-01

    Primary hyperhidrosis affects approximately 3% of the population and reduces quality of life in affected persons. Few studies have investigated the symptoms of anxiety, depression and hazardous alcohol consumption among those with hyperhidrosis and the effect of treatment with botulinum toxin. The first aim of this study was to investigate the effect of primary hyperhidrosis on mental and physical health, and alcohol consumption. Our second aim was to study whether and how treatment with botulinum toxin changed these effects. One hundred and fourteen patients answered questionnaires regarding hyperhidrosis and symptoms, including hyperhidrosis disease severity scale (HDSS), visual analog scale (VAS) 10-point scale for hyperhidrosis symptoms, hospital anxiety and depression scale (HADS), alcohol use disorder identification test (AUDIT) and short-form health survey (SF-36) before treatment with botulinum toxin and 2 weeks after. The age of onset of hyperhidrosis was on average 13.4 years and 48% described heredity for hyperhidrosis. Significant improvements were noted in patients with axillary and palmar hyperhidrosis regarding mean HDSS, VAS 10-point scale, HADS, SF-36 and sweat-related health problems 2 weeks after treatment with botulinum toxin. Changes in mean AUDIT for all participants were not significant. Primary hyperhidrosis mainly impairs mental rather than physical aspects of life and also interferes with specific daily activities of the affected individuals. Despite this, our patients did not show signs of anxiety, depression or hazardous alcohol consumption. Treatment with botulinum toxin reduced sweat-related problems and led to significant improvements in HDSS, VAS, HADS and SF-36 in our patients.

  6. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

    2016-04-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

  7. Kinetic and Reaction Pathway Analysis in the Application of Botulinum Toxin A for Wound Healing

    Directory of Open Access Journals (Sweden)

    Frank J. Lebeda

    2012-01-01

    Full Text Available A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical, surgical (incision wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxin's therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin.

  8. Botulinum toxin detection using AlGaN /GaN high electron mobility transistors

    Science.gov (United States)

    Wang, Yu-Lin; Chu, B. H.; Chen, K. H.; Chang, C. Y.; Lele, T. P.; Tseng, Y.; Pearton, S. J.; Ramage, J.; Hooten, D.; Dabiran, A.; Chow, P. P.; Ren, F.

    2008-12-01

    Antibody-functionalized, Au-gated AlGaN /GaN high electron mobility transistors (HEMTs) were used to detect botulinum toxin. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN /GaN HEMT drain-source current showed a rapid response of less than 5s when the target toxin in a buffer was added to the antibody-immobilized surface. We could detect a range of concentrations from 1to10ng/ml. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN /GaN HEMTs for botulinum toxin detection.

  9. Anatomy of the sweat glands, pharmacology of botulinum toxin, and distinctive syndromes associated with hyperhidrosis.

    Science.gov (United States)

    Kreyden, Oliver P; Scheidegger, E Paul

    2004-01-01

    For a long period the therapeutic modalities to treat focal hyperhidrosis (HH) were very limited. Due to this the problem of focal HH was delt with stepmotherly. Nowadays we can consider BTX as the therapy of choice for axillary HH after topical treatment with aluminium salts have failed. The amount of successful reports on botulinum toxin (BTX) in the treatment of focal HH brought a change and the interest for this specific disorder grew. This article gives details on anatomy and physiology of sweating and mechanism of BTX. Further distinctive syndromes associated with HH, which all can be treated with BTX like localized unilateral hyperhidrosis (LUH), Ross' Syndrome and Frey' Syndrome are presented. A diagnosis of primary HH is usually based on the patients's history, typical younger age and visible signs of excessive sweating. Before treatment it is important to objectify focal HH with performing sweat tests such like Minor starch test and/or gravimetry. The total number of sweat glands is somewhere between 2 and 4 million and only about 5% are active at the same time, indicating the enormous potential for sweat production. The eccrine sweat gland is a long-branched tubular structure with highly coiled secretory portion and a straight ductular portion. Sweat is produced by clear and dark cells and is a clear hypotonic, odorless fluid. In response to nerve impulses, Acetylcholine (ACh) is released from the presynaptic nerve endings and then binds to postsynaptic cholinergic receptors presumably present in the basolateral membrane of the clear cells. This activates a complex in- and efflux of electrolytes creating the hypotonic sweat. Injection of BTX leads to temporary chemodenervation with the loss or reduction of activity of the target organ. BTX is consisted of a heavy and a light chain. The structural architecture of BTX comprises three domains-L, H(N) and H(C)-each with a specific function in the mechanism of cell intoxication. The heavy chain is responsible

  10. Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases?

    Science.gov (United States)

    Marjoux, S; Brochard, C; Roman, S; Gincul, R; Pagenault, M; Ponchon, T; Ropert, A; Mion, F

    2015-01-01

    Endoscopic injections of botulinum toxin in the cardia or distal esophagus have been advocated to treat achalasia and spastic esophageal motility disorders. We conducted a retrospective study to evaluate whether manometric diagnosis using the Chicago classification in high-resolution manometry (HRM) would be predictive of the clinical response. Charts of patients with spastic and hypertensive motility disorders diagnosed with HRM and treated with botulinum toxin were retrospectively reviewed at two centers. HRM recordings were systematically reanalyzed, and a patient's phone survey was conducted. Forty-five patients treated between 2008 and 2013 were included. Most patients had achalasia type 3 (22 cases). Other diagnoses were jackhammer esophagus (8 cases), distal esophageal spasm (7 cases), esophagogastric junction outflow obstruction (5 cases), nutcracker esophagus (1 case), and 2 unclassified cases. Botulinum toxin injections were performed into the cardia only in 9 cases, into the wall of the distal esophagus in 19 cases, and in both locations (cardia and distal esophagus) in 17 cases. No complication occurred in 31 cases. Chest pain was noticed for less than 7 days in 13 cases. One death related to mediastinitis occurred 3 weeks after botulinum toxin injection. Efficacy was assessed in 42 patients: 71% were significantly improved 2 months after botulinum toxin, and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis; however, type 3 achalasia previously dilated and with normal integrated relaxation pressure (4s-integrated relaxation pressure botulinum toxin. Endoscopic injections of botulinum toxin may be effective in some patients with spastic or hypercontractile esophageal motility disorders. The manometric Chicago classification diagnosis does not seem to predict the results. Prospective randomized trials are required to identify patients most likely to benefit from

  11. Characterisation of botulinum toxins type C, D, E, and F by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

    NARCIS (Netherlands)

    Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

    2004-01-01

    In a follow-up of the earlier characterisation of botulinum toxins type A and B (BTxA and BTxB) by mass spectrometry (MS), types C, D, E, and F (BTxC, BTxD, BTxE, BTxF) were now investigated. Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent.

  12. Characterisation of botulinum toxins type C, D, E, and F by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

    NARCIS (Netherlands)

    Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

    2004-01-01

    In a follow-up of the earlier characterisation of botulinum toxins type A and B (BTxA and BTxB) by mass spectrometry (MS), types C, D, E, and F (BTxC, BTxD, BTxE, BTxF) were now investigated. Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. B

  13. Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin

    Directory of Open Access Journals (Sweden)

    Jasmin Weisemann

    2016-05-01

    Full Text Available Botulinum neurotoxins (BoNTs exhibit extraordinary potency due to their exquisite neurospecificity, which is achieved by dual binding to complex polysialo-gangliosides and synaptic vesicle proteins. The luminal domain 4 (LD4 of the three synaptic vesicle glycoprotein 2 isoforms, SV2A‐C, identified as protein receptors for the most relevant serotype BoNT/A, binds within the 50 kDa cell binding domain HC of BoNT/A. Here, we deciphered the BoNT/A‐SV2 interactions in more detail. In pull down assays, the binding of HCA to SV2-LD4 isoforms decreases from SV2C >> SV2A > SV2B. A binding constant of 200 nM was determined for BoNT/A to rat SV2C-LD4 in GST pull down assay. A similar binding constant was determined by surface plasmon resonance for HCA to rat SV2C and to human SV2C, the latter being slightly lower due to the substitution L563F in LD4. At pH 5, as measured in acidic synaptic vesicles, the binding constant of HCA to hSV2C is increased more than 10-fold. Circular dichroism spectroscopy reveals that the quadrilateral helix of SV2C-LD4 already exists in solution prior to BoNT/A binding. Hence, the BoNT/A‐SV2C interaction is of different nature compared to BoNT/B‐Syt-II. In particular, the preexistence of the quadrilateral β-sheet helix of SV2 and its pH-dependent binding to BoNT/A via backbone–backbone interactions constitute major differences. Knowledge of the molecular details of BoNT/A‐SV2 interactions drives the development of high affinity peptides to counteract BoNT/A intoxications or to capture functional BoNT/A variants in innovative detection systems for botulism diagnostic.

  14. Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin

    Science.gov (United States)

    Weisemann, Jasmin; Stern, Daniel; Mahrhold, Stefan; Dorner, Brigitte G.; Rummel, Andreas

    2016-01-01

    Botulinum neurotoxins (BoNTs) exhibit extraordinary potency due to their exquisite neurospecificity, which is achieved by dual binding to complex polysialo-gangliosides and synaptic vesicle proteins. The luminal domain 4 (LD4) of the three synaptic vesicle glycoprotein 2 isoforms, SV2A‐C, identified as protein receptors for the most relevant serotype BoNT/A, binds within the 50 kDa cell binding domain HC of BoNT/A. Here, we deciphered the BoNT/A‐SV2 interactions in more detail. In pull down assays, the binding of HCA to SV2-LD4 isoforms decreases from SV2C >> SV2A > SV2B. A binding constant of 200 nM was determined for BoNT/A to rat SV2C-LD4 in GST pull down assay. A similar binding constant was determined by surface plasmon resonance for HCA to rat SV2C and to human SV2C, the latter being slightly lower due to the substitution L563F in LD4. At pH 5, as measured in acidic synaptic vesicles, the binding constant of HCA to hSV2C is increased more than 10-fold. Circular dichroism spectroscopy reveals that the quadrilateral helix of SV2C-LD4 already exists in solution prior to BoNT/A binding. Hence, the BoNT/A‐SV2C interaction is of different nature compared to BoNT/B‐Syt-II. In particular, the preexistence of the quadrilateral β-sheet helix of SV2 and its pH-dependent binding to BoNT/A via backbone–backbone interactions constitute major differences. Knowledge of the molecular details of BoNT/A‐SV2 interactions drives the development of high affinity peptides to counteract BoNT/A intoxications or to capture functional BoNT/A variants in innovative detection systems for botulism diagnostic. PMID:27196927

  15. A three monoclonal antibody combination potently neutralizes multiple botulinum neurotoxin serotype F subtypes

    Science.gov (United States)

    Fan, Yongfeng; Garcia-Rodriguez, Consuelo; Lou, Jianlong; Wen, Weihua; Conrad, Fraser; Zhai, Wenwu; Smith, Theresa J.; Smith, Leonard A.

    2017-01-01

    Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4.06 × 10−9 M. By diversifying the V-regions of the lead mAbs and selecting for cross reactivity we generated five mAbs that bound each of the seven subtypes. Three scFv binding non-overlapping epitopes were converted to IgG that had KD for the different BoNT/F subtypes ranging from 2.2×10−8 M to 1.47×10−12 pM. An equimolar combination of the mAbs was able to potently neutralize BoNT/F1, F2, F4 and F7 in the mouse neutralization assay. The mAbs have potential utility as diagnostics capable of recognizing the known BoNT/F subtypes and could be developed as antitoxins to prevent and treat type F botulism. PMID:28323873

  16. Somatosensory evoked potentials of hand muscles in stroke and their modification by botulinum toxin: a preliminary study.

    Science.gov (United States)

    Basaran, Aynur; Emre, Ufuk; Karadavut, Kiymet Ikbal; Bulmus, Nercivan

    2012-06-01

    To determine the effect of botulinum toxin A on spasticity and somatosensory evoked potentials of hand muscles in patients who have undergone cerebrovascular accident. Preliminary, prospective, before-after study design. Six subjects prospectively followed after application of botulinum toxin A in the rehabilitation department of a university hospital. All patients underwent botulinum toxin A injection to the upper extremity muscles in varying combinations and carried out a home-based exercise programme. Primary outcome measure was median somatosensory evoked potential of hand muscles (N20). Secondary outcome measures were: spasticity assessed clinically by Modified Ashworth Scales (MAS); functional ability analysis assessed by Physician's Rating Scale (PRS); and functional difficulties reported by patients or their care-givers by patient disability and care-giver burden rating scale (PD & CBRS). MAS, PRS and PD & CBRS improved with botulinum toxin A treatment. In the affected limb, N20 potentials were impaired compared with those in the unaffected side. With botulinum toxin A treatment, although improvement in overall N20-P25 amplitudes was significant, as a result of limited sample size, post hoc pair-wise comparisons with Bonferroni correction failed to yield any significant pairs. The improvement in the median somatosensory evoked potentials following botulinum toxin A treatment suggests that central somatosensory patterns in hemiplegia can be modified by peripheral inputs.

  17. No clinical or neurophysiological evidence of botulinum toxin diffusion to non-injected muscles in patients with hemifacial spasm.

    Science.gov (United States)

    Lorenzano, C; Bagnato, S; Gilio, F; Fabbrini, G; Berardelli, A

    2006-04-01

    Botulinum toxin injected into a muscle may diffuse to nearby muscles thus producing unwanted effects. In patients with hemifacial spasm, we evaluated clinically and neurophysiologically, whether botulinum toxin type A (BoNT-A) diffuses from the injection site (orbicularis oculi) to untreated muscles (orbicularis oris from the affected side and orbicularis oculi and oris from the unaffected side). We studied 38 patients with idiopathic hemifacial spasm. Botulinum toxin was injected into the affected orbicularis oculi muscle alone (at 3 standardized sites) at a clinically effective dose. Patients were studied before (T0) and 3-4 weeks after treatment (T1). We evaluated the clinical effects of botulinum toxin and muscle strength in the affected and unaffected muscles. We also assessed the peak-to-peak amplitude compound muscle action potential (CMAP) recorded from the orbicularis oculi and orbicularis oris muscles on both sides after supramaximal electrical stimulation of the facial nerve at the stylomastoid foramen. In all patients, botulinum toxin treatment reduced muscle spasms in the injected orbicularis oculi muscle and induced no muscle weakness in the other facial muscles. The CMAP amplitude significantly decreased in the injected orbicularis oculi muscle, but remained unchanged in the other facial muscles (orbicularis oris muscle on the affected side and contra-lateral unaffected muscles). In conclusion, in patients with hemifacial spasm, botulinum toxin, at a clinically effective dose, induces no clinical signs of diffusion and does not reduce the CMAP size in the nearby untreated orbicularis oris or contralateral facial muscles.

  18. Botulinum toxin injection versus lateral internal sphincterotomy for chronic anal fissure: a meta-analysis of randomized control trials.

    Science.gov (United States)

    Chen, H-L; Woo, X-B; Wang, H-S; Lin, Y-J; Luo, H-X; Chen, Y-H; Chen, C-Q; Peng, J-S

    2014-08-01

    Although surgery is the gold standard treatment for anal fissure, the main concern remains its side effects and complications. Botulinum toxin injection and lateral internal sphincterotomy are technical options for patients suffering from chronic anal fissure. However, little is known about the efficacy of these two techniques. The aim of this meta-analysis was to compare the outcomes of botulinum toxin injection versus lateral internal sphincterotomy for chronic anal fissure. Original studies in English were searched from the MEDLINE database, PubMed, Web of Science, and the Cochrane Library database. Randomized control trials that compared botulinum toxin injection with lateral internal sphincterotomy were identified. Data were independently extracted for each study, and a meta-analysis was performed using fixed and random effects models. Four hundred and eighty-nine patients from seven trials met the inclusion criteria. Patients undergoing lateral internal sphincterotomy had a higher-healing and incontinence rate. No statistically significant differences were noted in total complications between botulinum toxin injection and lateral internal sphincterotomy. Patients treated with lateral internal sphincterotomy had a significantly lower recurrence rate than the patients treated with botulinum toxin injection. Our meta-analysis shows that lateral internal sphincterotomy was superior to botulinum toxin injection in terms of healing rate and lower recurrence rate. Botox, however, is safe associated with a lower rate of incontinence and could be used in certain situations. Further studies with a long-term follow-up are required to confirm our observations.

  19. Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

    Directory of Open Access Journals (Sweden)

    Jae Wook Kim

    2014-01-01

    Full Text Available Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group. Methods. Thirty patients with adductor spasmodic dysphonia (ADSD, who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P>0.05. There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

  20. Potential therapeutic effect of intravesical botulinum toxin type A on bladder pain syndrome/interstitial cystitis.

    Science.gov (United States)

    Jhang, Jia-Fong; Jiang, Yuan-Hong; Kuo, Hann-Chorng

    2014-04-01

    Bladder pain syndrome/interstitial cystitis is characterized by bladder pain associated with urgency, frequency, nocturia, dysuria and sterile urine. Recent studies have shown that these bladder dysfunctions could originate from chronic inflammation or urothelial insult and proceed to a cascade of tissue reactions, which finally ascends to the central nervous system. Pilot studies of intravesical injection of botulinum toxin type A for bladder pain syndrome/interstitial cystitis had been introduced since 2005 with a promising result. Recent evidence suggests that botulinum toxin type A could significantly improve symptoms such as daytime frequency, nocturia, pain, quality of life and bladder capacity in bladder pain syndrome/interstitial cystitis patients. Single injection of botulinum toxin could not achieve long-term successful therapeutic result, and repeat injections could provide a better long-term success rate. However, patients with ulcer type bladder pain syndrome/interstitial cystitis might not gain a benefit from botulinum toxin type A injection. Laboratory evidence showed that botulinum toxin type A for bladder pain syndrome/interstitial cystitis injection could induce peripheral desensitization, reduces bladder chronic inflammation and decreases apoptotic signal molecules in the urothelium. The present article reviewed the recent advances of botulinum toxin type A on bladder pain syndrome/interstitial cystitis.

  1. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

    Science.gov (United States)

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-12-01

    Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures.

  2. Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B

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    Luisa W. Cheng

    2015-11-01

    Full Text Available Botulinum neurotoxins (BoNT are some of nature’s most potent toxins. Due to potential food contamination, and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are of urgent interest. Recently, we have developed a sensitive electrochemiluminescent (ECL immunoassay for BoNT/B, using monoclonal antibodies (mAbs MCS6-27 and anti-BoNT/B rabbit polyclonal antibodies as the capture and detector. The ECL assay detected as little as 1 pg/mL BoNT/B in the buffer matrix, surpassing the detection sensitivities of the gold standard mouse bioassays. The ECL assay also allowed detection of BoNT/B in sera matrices of up to 100% sera with negligible matrix effects. This highly-sensitive assay allowed the determination of the biological half-lives of BoNT/B holotoxin in vivo. We further tested the toxin neutralization potential of our monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs protected mice in both pre- and post-exposure models to lethal doses of BoNT/B. MAbs were capable of increasing survival of animals when administered even 10 h post-intoxication in an oral model, suggesting a likely time for BoNT/B complexes to reach the blood stream. More sensitive detection assays and treatments against BoNT intoxication will greatly enhance efforts to combat botulism.

  3. Multipoint and multilevel injection technique of botulinum toxin A in facial aesthetics.

    Science.gov (United States)

    Iozzo, Ivano; Tengattini, Vera; Antonucci, Valentina A

    2014-06-01

    Botulinum toxin represents one of the most frequently requested cosmetic procedures. We treated 223 patients with facial wrinkles using a new technique of injection of botulinum toxin A (BTA) called multipoint and multilevel injection technique (MMIT). The aim of MMIT was to relax the muscle and not paralyze it. Patient satisfaction was evaluated by Facial Line Treatment Satisfaction Questionnaire (FTSQ). Treatment with botulinum toxin determined a good response in all patients. Facial rhytids were completely resolved in case of young skin and well reduced in case of aged skin, leaving a natural aspect both in static and dynamic wrinkles. Patient mean overall satisfaction evaluated with FTSQ was 6.4 ± 1.1. In our experience, the use of botulin toxin by MMIT consents a better calibration of action with a soft and natural result. This can be achieved by distributing the BTA dose through various injection points for each area ("multipoint injections"). Furthermore, injections can be performed at different levels ("multilevel injections"). The level of injections regulates the potency of effect on the muscle: if the level is deep (intramuscular), the effect will be strong while if it is medium or superficial (subcutaneous and intradermal), the effect will be soft. This consents a fine calibration of action on muscle activity with a personal aesthetic result.

  4. Evaluation of the therapeutic use of botulinum toxin A in the periorbital region

    Directory of Open Access Journals (Sweden)

    Ahmed Tawfik

    2015-01-01

    Full Text Available Botulinum toxin blocks acetylcholine release at the neuromuscular junction causing paralysis that is reversed within 4 months. The toxin was well known for its lethal effect when ingested with food (botulism; however, it was found to be highly effective in various disorders, both cosmetic and noncosmetic. The therapeutic uses in ophthalmology include treatment of strabismus, spastic focal facial dystonias, induction of temporary ptosis in cases of lagophthalmos (chemotarsorrhaphy, temporary correction of dysthyroid upper eyelid retraction, suppression of lacrimal gland secretion to temporarily control gustatory lacrimation, some cases of obstructive epiphora and primary hyperlacrimation, and temporary correction of lower lid entropion. In this prospective study, we evaluate the results of using botulinum toxin A (botox injection in some periorbital pathologies namely, focal facial dystonias, lower lid entropion, lagophthalmos, and epiphora. Fifty patients were treated with botox (20 patients with focal facial dystonias, nine with lagophthalmos, eight with lower lid entropion, and 13 with epiphora, different techniques were used according to the pre-existing pathology, and the following data were recorded: age and sex, total dose for each injection, onset and duration of effect, degree of improvement, and the occurrence of any adverse effects. The study results supported the high efficacy of botulinum toxin for treatment of blepharospasm, hemifacial spasm, lagophthalmos, lower lid entropion, and epiphora, with marked to moderate improvement in 99, 87.5, 55.5, 75, and 92.3% of patients, respectively. Few side effects occurred but they resolved spontaneously without residues. We concluded that botulinum toxin A is a safe and effective treatment with a temporary outcome that may be desirable in certain situations.

  5. Beneficial effects of botulinum toxin type A in trigeminal neuralgia Beneficio de la toxina botulínica tipo A en neuralgia del trigemino

    OpenAIRE

    Carlos Zúñiga; Sergio Díaz; Fabián Piedimonte; Federico Micheli

    2008-01-01

    Botulinum toxin has been thoroughly studied as a potential tool in the treatment of several pain syndromes. Therefore, we assessed the clinical effects of botulinum toxin type A injections in 12 patients with otherwise unresponsive idiopathic trigeminal neuralgia. Patients were infiltrated with 20-50 units of botulinum toxin in trigger zones. Those who presented with mandibular involvement were also infiltrated in the masseter muscle. The patients were assessed on a weekly basis using the Vis...

  6. Tetanus Toxin and Botulinum Toxin A Utilize Unique Mechanisms To Enter Neurons of the Central Nervous System

    OpenAIRE

    Blum, Faith C.; Chen CHEN; Kroken, Abby R.; Barbieri, Joseph T

    2012-01-01

    Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most toxic proteins for humans. While BoNTs cause flaccid paralysis, TeNT causes spastic paralysis. Characterized BoNT serotypes enter neurons upon binding dual receptors, a ganglioside and a neuron-specific protein, either synaptic vesicle protein 2 (SV2) or synaptotagmin, while TeNT enters upon binding gangliosides as dual receptors. Recently, TeNT was reported to enter central nervous system (CNS) neurons upon synaptic ves...

  7. Iterative structure-based peptide-like inhibitor design against the botulinum neurotoxin serotype A.

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    Jorge E Zuniga

    Full Text Available The botulinum neurotoxin serotype A light chain (BoNT/A LC protease is the catalytic component responsible for the neuroparalysis that is characteristic of the disease state botulism. Three related peptide-like molecules (PLMs were designed using previous information from co-crystal structures, synthesized, and assayed for in vitro inhibition against BoNT/A LC. Our results indicate these PLMS are competitive inhibitors of the BoNT/A LC protease and their K(i values are in the nM-range. A co-crystal structure for one of these inhibitors was determined and reveals that the PLM, in accord with the goals of our design strategy, simultaneously involves both ionic interactions via its P1 residue and hydrophobic contacts by means of an aromatic group in the P2' position. The PLM adopts a helical conformation similar to previously determined co-crystal structures of PLMs, although there are also major differences to these other structures such as contacts with specific BoNT/A LC residues. Our structure further demonstrates the remarkable plasticity of the substrate binding cleft of the BoNT/A LC protease and provides a paradigm for iterative structure-based design and development of BoNT/A LC inhibitors.

  8. Botulinum neurotoxin serotype A specific cell-based potency assay to replace the mouse bioassay.

    Science.gov (United States)

    Fernández-Salas, Ester; Wang, Joanne; Molina, Yanira; Nelson, Jeremy B; Jacky, Birgitte P S; Aoki, K Roger

    2012-01-01

    Botulinum neurotoxin serotype A (BoNT/A), a potent therapeutic used to treat various disorders, inhibits vesicular neurotransmitter exocytosis by cleaving SNAP25. Development of cell-based potency assays (CBPAs) to assess the biological function of BoNT/A have been challenging because of its potency. CBPAs can evaluate the key steps of BoNT action: receptor binding, internalization-translocation, and catalytic activity; and therefore could replace the current mouse bioassay. Primary neurons possess appropriate sensitivity to develop potential replacement assays but those potency assays are difficult to perform and validate. This report describes a CBPA utilizing differentiated human neuroblastoma SiMa cells and a sandwich ELISA that measures BoNT/A-dependent intracellular increase of cleaved SNAP25. Assay sensitivity is similar to the mouse bioassay and measures neurotoxin biological activity in bulk drug substance and BOTOX® product (onabotulinumtoxinA). Validation of a version of this CBPA in a Quality Control laboratory has led to FDA, Health Canada, and European Union approval for potency testing of BOTOX®, BOTOX® Cosmetic, and Vistabel®. Moreover, we also developed and optimized a BoNT/A CBPA screening assay that can be used for the discovery of novel BoNT/A inhibitors to treat human disease.

  9. Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kumar G.; Swaminathan S.; Kumaran, D.; Ahmed, S. A.

    2012-05-01

    Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC{sub 50} of 0.9 {micro}M and a K{sub i} of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.

  10. Combined Effect Of Botulinum Toxin And Splinting On Motor Components And Function Of People With Stroke

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    Aryan Shamili

    2017-02-01

    Full Text Available Background and objective: Spasticity is one of the problems following stroke. Due to this increase in muscle tone, patients are confronted to problems in motor control and difficulties in activities of daily living and complications such as shortness and contracture. The aim of this study was to examine the effects of Simultaneous use of both splint and botulinum toxin-A (BTX-A injection on spasticity, range of motion and upper extremity function in a 3-month period. Methods: The design of this study was a comparison between 3 groups of interventions, conducted in rehabilitation clinics in Tehran. Sixty people with chronic stroke were recruited. Based on the inclusion criteria, a total of 39 stroke patients after completing the consent forms were entered to intervention groups; splint or botulinum toxin injection or combined splint/botulinum toxin injection. They were followed up about 3 months and the evaluations were done monthly. Goniometry was the method to measure range of motion, and Modified Ashworth scale was used to examine the spasticity and the upper extremity function was scored based on Fugl-Meyer assessment.   Statistical analysis was done using SPSS 17. And ANOVAs was used for comparison between groups and times.  Significance was set at 0.05. Results: All outcome measures improved within each group but the differences between splint group and BTX-A group and the BTX-A-splint group was not significant in most outcomes during 3 periods (first evaluation until end of the first month, the end of first month until the end of second month, the end of second month until the end of the third month (p> 0 / 05. The results also showed that the changes in elbow`s spasticity {p= 0.05} and wrist`s spasticity {p= 0.007} and upper extremity function { p = 0.04} were obvious between the three groups over the 3-months and the difference in the group of combined use of botulinum toxin and splint was more than other groups. Conclusion: In this

  11. Influence of botulinum C2 toxin on F-actin and N-formyl peptide receptor dynamics in human neutrophils

    Science.gov (United States)

    1989-01-01

    Stimulation of human neutrophils with the chemotactic N-formyl peptide causes production of oxygen radicals and conversion of monomeric actin (G-actin) to polymeric actin (F-actin). The effects of the binary botulinum C2 toxin on the amount of F-actin and on neutrophil cell responses were studied. Two different methods for analyzing the actin response were used in formyl peptide-stimulated cells: staining of F- actin with rhodamine-phalloidin and a transient right angle light scatter. Preincubation of neutrophils with 400 ng/ml component I and 1,600 ng/ml component II of botulinum C2 toxin for 30 min almost completely inhibited the formyl peptide-stimulated polymerization of G- actin and at the same time decreased the amount of F-actin in unstimulated neutrophils by an average of approximately 30%. Botulinum C2 toxin preincubation for 60 min destroyed approximately 75% of the F- actin in unstimulated neutrophils. Right angle light scatter analysis showed that control neutrophils exhibited the transient response characteristic of actin polymerization; however, after botulinum C2 toxin treatment, degranulation was detected. Single components of the binary botulinum C2 toxin were without effect on the actin polymerization response. Fluorescence flow cytometry and fluorospectrometric binding studies showed little alteration in N- formyl peptide binding or dissociation dynamics in the toxin-treated cells. However, endocytosis of the fluorescent N-formyl peptide ligand- receptor complex was slower but still possible in degranulating neutrophils treated with botulinum C2 toxin for 60 min. The half-time of endocytosis, estimated from initial rates, was 4 and 8 min in control and botulinum C2 toxin-treated neutrophils, respectively. PMID:2768337

  12. Long-term quantitative benefits of botulinum toxin type A in the treatment of axillary hyperhidrosis.

    Science.gov (United States)

    Odderson, Ib R

    2002-06-01

    Although axillary hyperhidrosis is readily treated with botulinum toxin, the time course of benefits is not well established. To quantify the long-term effectiveness of botulinum toxin type A (BTX-A) for the treatment of axillary hyperhidrosis. This was a double-blind, placebo-controlled study. Eighteen patients received intradermal injections of either 100 U BTX-A (50 U/ml/axilla) or placebo. Sweating per surface area was quantified monthly for 5 months. The BTX-A group had an average reduction in sweat production of 91.6% at 2 weeks (from 5.03 ml/min/m(2) to 0.42 ml/min/m(2), P BTX-A-treated patients had returned to baseline sweat production. These quantitative results demonstrate that BTX-A is a safe and effective treatment for axillary hyperhidrosis and that the benefits last for at least 5 months.

  13. The use of botulinum toxin in head and face medicine: An interdisciplinary field

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    Laskawi Rainer

    2008-03-01

    Full Text Available Abstract Background In this review article different interdisciplinary relevant applications of botulinum toxin type A (BTA in the head and face region are demonstrated. Patients with head and face disorders of different etiology often suffer from disorders concerning their musculature (example: synkinesis in mimic muscles or gland-secretion. This leads to many problems and reduces their quality of life. The application of BTA can improve movement disorders like blepharospasm, hemifacial spasm, synkinesis following defective healing of the facial nerve, palatal tremor, severe bruxism, oromandibular dystonias hypertrophy of the masseter muscle and disorders of the autonomous nerve system like hypersalivation, hyperlacrimation, pathological sweating and intrinsic rhinitis. Conclusion The application of botulinum toxin type A is a helpful and minimally invasive treatment option to improve the quality of life in patients with head and face disorders of different quality and etiology. Side effects are rare.

  14. Effect of rehabilitation and botulinum toxin injection on gait in chronic stroke patients: a randomized controlled study.

    Science.gov (United States)

    Roche, Nicolas; Zory, Raphaël; Sauthier, Antoine; Bonnyaud, Celine; Pradon, Didier; Bensmail, Djamel

    2015-01-01

    Botulinum toxin injections are used to treat spasticity in stroke. Although this treatment is effective on muscle tone, its effect on functional gait-related activities remains uncertain. The aim of this randomized controlled trial was to determine the effect of a self-rehabilitation programme as an adjunct to botulinum toxin injections on gait-related activities in patients with chronic hemiparesis. Thirty-five outpatients were included. Each patient was randomized to 1 of 2 groups: botulinum toxin + standardized self-rehabilitation programme (R group, n = 19) or botulinum toxin alone (C group, n = 16). Each patient was evaluated with the following tests before botulinum toxin injections and one month afterwards: 10-m timed walk, Timed Up and Go, distance covered in 6 min over an ecological circuit, and the stair test. There were significant improvements in the R group compared with the C group: maximal gait speed improved by 8% (p = 0.003); distance covered in 6 min over an ecological circuit increased by 7.1% (p = 0.01); and time to ascend and to descend a flight of stairs decreased by 9.8% (p = 0.003) and 6.6% (p = 0.009), respectively. The self-rehabilitation programme was well tolerated and safe. These results strongly suggest that a standardized self-rehabilitation programme constitutes a useful adjunct to botulinum toxin injections in order to improve gait-related activities.

  15. Analysis of the mechanisms that underlie absorption of botulinum toxin by the inhalation route.

    Science.gov (United States)

    Al-Saleem, Fetweh H; Ancharski, Denise M; Joshi, Suresh G; Elias, M; Singh, Ajay; Nasser, Zidoon; Simpson, Lance L

    2012-12-01

    Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers.

  16. Sensing the Deadliest Toxin: Technologies for Botulinum Neurotoxin Detection

    OpenAIRE

    Čapek, Petr; Dickerson, Tobin J.

    2010-01-01

    Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently develop...

  17. Botulinum Toxin Treatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea.

    Science.gov (United States)

    Hosp, Christine; Naumann, Markus K; Hamm, Henning

    2016-02-01

    Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient.

  18. Autonomic function after botulinum toxin type A or B: a double-blind, randomized trial.

    Science.gov (United States)

    Tintner, R; Gross, R; Winzer, U F; Smalky, K A; Jankovic, J

    2005-09-13

    To compare autonomic effects of botulinum toxin (BTX), we randomized patients with cervical dystonia to receive either BTX-A or BTX-B in a double-blind manner. Efficacy and physiologic questionnaire measures of autonomic function were assessed at baseline and 2 weeks after injection. Patients treated with BTX-B had less saliva production (p BTX-A, but did not differ in other tests of autonomic functions.

  19. Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain

    OpenAIRE

    Young Eun Moon; Jung Hyun Choi; Hue Jung Park; Ji Hye Park; Ji Hyun Kim

    2016-01-01

    Neuropathic pain includes postherpetic neuralgia (PHN), painful diabetic neuropathy (PDN), and trigeminal neuralgia, and so on. Although various drugs have been tried to treat neuropathic pain, the effectiveness of the drugs sometimes may be limited for chronic intractable neuropathic pain, especially when they cannot be used at an adequate dose, due to undesirable severe side effects and the underlying disease itself. Botulinum toxin type A (BoNT-A) has been known for its analgesic effect in...

  20. Jaw-opening oromandibular dystonia secondary to Wilson's Disease treated with botulinum toxin type A

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2012-06-01

    Full Text Available We have reported a case series of five patients with jaw-opening oromandibular dystonia secondary to Wilson's disease (WD, in which the patients were treated with botulinum toxin type A (BTX-A. In all cases, dystonia score was partially reduced three weeks after injections. The most common side effect was transient mild dysphagia. This preliminary study showed that jaw-opening oromandibular dystonia in WD may be partially responsive to the use of BTX-A.

  1. Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review

    OpenAIRE

    Oliveira Filho,Ademar Francisco de; Silva,Gêssyca Adryene de Menezes; Almeida,Débora Milenna Xavier

    2016-01-01

    ABSTRACT Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of ...

  2. Efficacy of type a botulinum toxin injections and infrared polarized light on treating chronic migraine.

    Science.gov (United States)

    Song, J-H; Zhang, G-B; Ding, X-D; Huang, L; Hong, Y; Chen, H-X

    2015-01-01

    To investigate the clinical value of the combination of ultrasound-and-hyponome-guided type A botulinum toxin injection and infrared polarized light on treating chronic migraine. Ninety-one patients with chronic migraine were randomly divided into four groups: in the control group (group A, 22 cases in total), nimodipine was used in the treatment of chronic migraine for two months; in the infrared polarized light therapy group (group B, 22 cases in total), infrared polarized light was adopted in the treatment of chronic migraine for 50-60d; in the botulinum toxin treatment group (group C, 24 cases in total), ultrasound-and-hyponome-guided type A botulinum toxin was injected into frontal, temporal, and occipital muscles in treating chronic migraine; in the joint treatment group (group D, 23 cases in total), ultrasound-and-hyponome-guided type A botulinum toxin injection in group C and infrared polarized light in group B were both used here in the treatment of chronic migraine. Infrared polarized light therapy lasted 50-60d and the time of study lasted six months. The survey would include the conditions of patients with chronic migraine three months before treatment and at one, three and six months after treatment. Patients were asked to fill the MIDAS (migraine disability assessment questionnaire) and were graded on the evaluation scale of life quality, so that the researchers would be able to compare attack frequency, duration of attack, attack severity, the use of painkillers and their recovery from chronic migraine, and then observe their adverse reactions. Eleven cases dropped out during the treatment, three cases in A group, two cases in group B, four cases in group C and two cases in group D. One, three and six months after treatment, the MIDAS scores in group A, B, C and D were significantly lower than before the treatment. Hence, the differences were statistically significant (p polarized light on treating chronic migraine demonstrated a significant clinical

  3. Assessment of intralesional injection of botulinum toxin type A injection for hypertrophic scars

    Directory of Open Access Journals (Sweden)

    Alhasan M Elhefnawy

    2016-01-01

    Full Text Available Background: Hypertrophic scars are dermal fibroproliferative disorders that typically develop after a skin injury heals. They can cause physical, psychological, and cosmetic problems. The management of such scars remains a matter of debate due to lack of effective treatment methods and the inability to prevent recurrences. Recent reports have demonstrated that botulinum toxin type A improves wound healing so it may play a role in treating hypertrophic scars. Aims: We assessed the effectiveness of intralesional botulinum toxin type A injection for treating hypertrophic scars. Methods: This prospective clinical study included twenty patients with hypertrophic scars. Intralesional injection of botulinum toxin type A was given once a month for three months with a follow-up period of six months. Each lesion was injected until slight blanching occurred. Therapeutic satisfaction of the patient and physician were recorded. Lesions were assessed for erythema, itching and pliability. Each item was assessed on a 5-point scale. Results: Therapeutic satisfaction was recorded as 'good' in 14 patients and 'excellent' in the remaining six. The mean erythema score decreased from 3.2 to 1.0, the mean pliability score from 3.3 to 0.8 and the mean itching score from 2.7 to 0.7. All of these were statistically significant. Limitations: A larger sample size and longer follow-up period would have given a better evaluation but was not feasible due to the high expenses involved. Conclusion: Botulinum toxin type A is a novel and promising therapy for hypertrophic scars with few side effects.

  4. Clinical and image improvement of Raynaud's phenomenon after botulinum toxin type A treatment.

    Science.gov (United States)

    Zhao, HongMei; Lian, YaJun

    2015-08-01

    Raynaud's phenomenon is often accompanied by pain, digital ulceration and compromised daily activities. Pharmacological therapy or sympathectomies have been administered to diminish these symptoms but existing treatments are not invariably efficacious. A recent case series has described the use of botulinum toxin type A in the treatment of Raynaud's phenomenon. We report two patients with severe or mild Raynaud's phenomenon who were injected with BTX-A; both of whom experienced clinical and image improvement after treatment.

  5. Altered cortical activation from the hand after facial Botulinum Toxin treatment

    OpenAIRE

    Haenzi, Sara; Stefanics, Gabor; Lanaras, Tatjana; Calcagni, Maurizio; Ghosh, Arko

    2014-01-01

    Plastic interactions between face and hand cortical tactile circuits occur after severe injuries that affect the hand such as in amputation or spinal cord injury. However, whether loss of facial movements alters the cortical circuits involved in processing tactile inputs from the hand remains unknown. In this prospective observational study we used electroencephalography (EEG) to measure cortical activity evoked by tactile stimulation of the hands before and after botulinum toxin-A-induced fa...

  6. Botulinum toxin type A treatment of cerebral palsy: an integrated approach

    OpenAIRE

    Molenaers, Guy; Desloovere, Kaat; Eyssen, M; De Cat, Josse; Jonkers, Ilse; De Cock, Paul

    1999-01-01

    We have applied a multilevel approach no the management of spasticity associated with cerebral palsy (CP). All of the following factors are important in forming an integrated strategy for botulinum toxin type A (BTX-A) therapy: the timing of injections, patient selection, multilevel BTS-A treatment, optimal dosage and injection technique, follow-up treatment and objective measurements of functional outcome. Data on all these factors are presented here. CP patients had a mean age of 6.5 years ...

  7. Botulinum Toxin Treatment of Blepharospasm, Orofacial/Oromandibular Dystonia, and Hemifacial Spasm.

    Science.gov (United States)

    Karp, Barbara Illowsky; Alter, Katharine

    2016-02-01

    Blepharospasm is a focal dystonia characterized by involuntary, repetitive eye closure. Orofacial and oromandibular dystonia describe involuntary dystonic movements of orofacial and oromandibular musculature. Hemifacial spasm is characterized by repetitive synchronous contraction of facial nerve innervated muscles on one side of the face. In this article, the clinical presentation, epidemiology, and approaches to treatment are reviewed. Technical aspects of using botulinum toxin for treatment and reported outcomes are discussed.

  8. Botulinum toxin injection to facilitate rehabilitation of muscle imbalance syndromes in sports medicine.

    Science.gov (United States)

    Cullen, D M; Boyle, J J W; Silbert, P L; Singer, B J; Singer, K P

    2007-12-15

    Intramuscular injection of Botulinum toxin to produce reduction of focal muscle overactivity, and localized muscle spasm, has been utilized therapeutically for almost two decades. Muscle overactivity in neurologically normal muscle, where an imbalance exists between a relatively overactive muscle and its less active synergist or antagonist, can inhibit control of the antagonist producing a functional muscle imbalance. This brief review provides an overview of the role of muscle imbalance in sports-related pain and dysfunction, and outlines the potential for intramuscular injection of Botulinum toxin to be used as an adjunct to specific muscle re-education and functional rehabilitation in this patient group. A comprehensive understanding of normal movement and the requirements of the sporting activity are essential to allow accurate diagnosis of abnormal motor patterns and to re-educate more appropriate movement strategies. Therapeutic management of co-impairments may include stretching of tight soft tissues, specific re-education aimed at isolation of the non-dominant weak muscles and improvement in their activation, 'unlearning' of faulty motor patterns, and eventual progression onto functional exercises to anticipate gradual return to sporting activity. Intramuscular injection of Botulinum toxin, in carefully selected cases, provides short term reduction of focal muscle overactivity, and may facilitate activation of relatively 'inhibited' muscles and assist the restoration of more appropriate motor patterns.

  9. Botulinum Toxin as a Novel Addition to Anti-Arthritis Armamentarium

    Directory of Open Access Journals (Sweden)

    Hamid Namazi

    2005-01-01

    Full Text Available Osteoarthritis is the most common joint disease and is among the most frequent health problems for middle aged and older people. There is strong evidence that proinflammatory cytokines contribute to cartilage degradation in osteoarthritis. Interleukin-1 is the prototypical proinflammatory cytokine implicated in the pathogenesis of cartilage matrix degeneration. Results from studies in animal models provide stronger evidence implicating a role for interleukin-1 in the pathogenesis of matrix loss in osteoarthritis. These include the induction of proteoglycan loss by intraarticular injection of interleukin-1 and the capacity of the inhibitor of interleukin-1, interleukin-1 receptor antagonist (IL-1 ra, to slow the progression of cartilage loss in animal models of osteoarthritis. The botulinum toxin has been used in many clinical situations such as: cerebral palsy, headache, cosmesis and etc. Moreover, there is evidence that botulinum toxin specifically inhibits Rho GTPase by ADP-ribosylation of aminoacid ASn-41. Rho GTPase is necessary for activation of interleukin-1 inflammation pathway. Based on previously mentioned evidence we suggest, intraarticular injection of the botulinum toxin may be a useful therapy in osteoarthritis.

  10. Intravesical Botulinum Toxin for Persistent Autonomic Dysreflexia in a Pediatric Patient

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    Gina Lockwood

    2016-01-01

    Full Text Available Introduction. We present a novel case of persistent autonomic dysreflexia in a pediatric spinal cord injury patient treated successfully with intravesical botulinum toxin. Study Design. A retrospective chart review of one patient seen at the Children’s Hospital of Wisconsin from 2006 to 2012 was performed. Results. A pediatric spinal cord injury patient with known neurogenic bladder presented with severe hypertension consistent with autonomic dysreflexia. His symptoms and hypertension did not improve with conservative measures, and he necessitated ICU admission and antihypertensive drips. He was taken to the operating room for intravesical botulinum toxin for refractory bladder spasms. Following this, his symptoms abated, and he was weaned off IV antihypertensives and returned to his baseline state. His symptoms were improved for greater than six months. Conclusions. There are few treatment options for the management of refractory autonomic dysreflexia. Intravesical botulinum toxin has never been reported for this use. Dedicated research is warranted to assess its efficacy, as it was used successfully to abort autonomic dysreflexia in this patient.

  11. The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain.

    Science.gov (United States)

    Singer, Barbara J; Silbert, Benjamin I; Silbert, Peter L; Singer, Kevin P

    2015-08-25

    Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional "denervation" which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.

  12. A Beautician’s Dystonia: Long-Lasting Effect of Botulinum Toxin

    Directory of Open Access Journals (Sweden)

    Siria Di Martino

    2014-01-01

    Full Text Available Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders. Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin into the extensor digitorum communis (35 U, flexor carpi radialis (35 U, and flexor digitorum superficialis (30 U muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment. In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients’ ability to work and quality of life.

  13. Effect of Botulinum Toxin on Disabling Neuropathic Pain: A Case Presentation Suggesting a New Therapeutic Strategy.

    Science.gov (United States)

    Buonocore, Michelangelo; Demartini, Laura; Mandrini, Silvia; Dall'Angelo, Anna; Dalla Toffola, Elena

    2017-02-01

    This case presentation describes a 47-year-old woman who developed complex regional pain syndrome type II with severe neuropathic pain following iatrogenic transection of the tibial nerve at the ankle. The pain and disability progressively worsened over time, markedly impaired ambulation, and were not relieved despite various analgesic treatments. After injection of botulinum toxin (abobotulinumtoxinA, BoNT-A) in the leg muscles the tendons of which pass through the tarsal tunnel (together with the tibial nerve), her pain decreased and her walking capacity improved. This case suggests a new therapeutic role for botulin toxin in treating peripheral neuropathic pain caused by movement-evoked ectopic potentials.

  14. Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes.

    Science.gov (United States)

    Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J

    2013-03-19

    Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

  15. Novel use of botulinum toxin to ameliorate arthrofibrosis: an experimental study in rabbits.

    Science.gov (United States)

    Namazi, Hamid; Torabi, Simin

    2007-08-01

    This study aimed to investigate the effects of intra-articular botulinum toxin in preventing arthrofibrosis. Arthrofibrosis was induced in both stifle joints of 20 rabbits by transecting the anterior cruciate ligament under intramuscular anesthesia with ketamine and xylazine. Intra-articular toxin at a dose of 0.6 ml (50 unit) and physiologic saline solution (0.6 ml) were injected into the right and left stifle joints, respectively, 3 times with a 1-week interval between each injection. The rabbits were euthanized in the 12th week via high dose anesthesia to remove the stifle joint. The severity of adhesions was assessed, applying a universal scoring system. Also the stifle joints were histologically evaluated for fibrosis. With regards to severity of adhesion a significant reduction in the adhesion score was observed in the toxin-treated group in comparison to untreated controls with mean +/- SE values of 0.2 +/- 0.1 and 2.4 +/- 0.2, respectively (p < 0.01). The histological evaluation showed no significant fibroblast in the toxin-treated group versus dense fibers with mature fibroblasts in the control group. Our results suggest that botulinum toxin demonstrated efficacy in preventing adhesion after knee surgery and all the parameters monitored showed consistent statistically significant improvement.

  16. Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.

    Science.gov (United States)

    Chellapandi, P; Prisilla, A

    2016-12-01

    Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines. C2 toxin is a binary toxin that consists of a catalytic subunit (C2I) and a translocation subunit (C2II). C2I component is structurally and functionally similar to the VIP2 and iota A toxin whereas C2II component shows a significant homology with the protective antigen from anthrax toxin and iota B. Unlike C2 toxin, C3 toxin is devoid of translocation/binding subunit. Extensive studies on their sequence-structure-function link spawn additional efforts to understand the catalytic mechanisms and target recognition. Structural and functional relationships of them are often determined by using evolutionary constraints as valuable biological measures. Enzyme-deficient mutants derived from these toxins have been used as drug/protein delivery systems to eukaryotic cells. Thus, current knowledge on their molecular diversity is a well-known perspective to design immunotoxin or subunit vaccine for C. botulinum infection.

  17. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

    Energy Technology Data Exchange (ETDEWEB)

    Rose, S.A.; Bailey, N.E.; Stringer, M.F. (Campden Food and Drink Research Association, Chipping Campden (UK)); Modi, N.K.; Tranter, H.S. (Porton International plc., London (UK)); Hambleton, P. (Centre for Applied Microbiological Research, Porton Down (UK))

    1988-10-01

    The effects of irradiation of Clostridium botulinum neurotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author).

  18. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus

    Energy Technology Data Exchange (ETDEWEB)

    Rose, S.A.; Bailey, N.E.; Stringer, M.F. (Campden Food and Drink Research Association, Chipping Campden (UK)); Modi, N.K.; Tranter, H.S. (Centre for Applied Micobiological Research, Porton Down, (UK)); Hambleton, P. (Porton International plc, London (UK))

    1989-09-01

    The effects of irradiation of Clostridium botulinum neutotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. (author).

  19. Production and evaluation of a recombinant subunit vaccine against botulinum neurotoxin serotype B using a 293E expression system.

    Science.gov (United States)

    Yu, YunZhou; Shi, DanYang; Liu, Si; Gong, Zheng-Wei; Wang, Shuang; Sun, ZhiWei

    2015-01-01

    Although Escherichia coli and yeast were commonly used to express recombinant Hc of botulinum neurotoxins, as an alternative, in current study, a 293E expression system was used to express the Hc of botulinum neurotoxin serotype B (BHc) as soluble recombinant protein for experimental vaccine evaluation. Our results demonstrated that the 293E expression system could produce high level of recombinant secreted BHc protein, which was immunorecognized specifically by anti-botulinum neurotoxin serotype B (BoNT/B) sera and showed ganglioside binding activities. The serological response and efficacy of recombinant BHc formulated with aluminum hydroxide adjuvant were evaluated in mice. Immunization with Alhydrogel-formulated BHc subunit vaccine afforded the effective protection against BoNT/B challenge. A frequency- and dose-dependent effect to immunization with BHc subunit vaccine was observed and the ELISA antibody titers correlated well with neutralizing antibody titers and protection. And a solid-phase assay showed that the neutralizing antibodies from the BHc-immunized mice inhibited the binding of BHc to the ganglioside GT1b. Our results also show that the plasmid pABE293SBHc derived of the 293E expression system as DNA vaccine is capable of inducing stronger humoral response and protective efficacy against BoNT/B than the pVAX1SBHc. In summary, immunization with the 293E-expressed BHc protein generates effective immune protection against BoNT/B as E. coli or yeast-expressed BHc, so the efficient expression of botulinum Hc protein for experimental vaccine can be prepared using the 293E expression system.

  20. Multivalent Chromosomal Expression of the Clostridium botulinum Serotype A Neurotoxin Heavy-Chain Antigen and the Bacillus anthracis Protective Antigen in Lactobacillus acidophilus

    Science.gov (United States)

    Klaenhammer, Todd R.

    2016-01-01

    ABSTRACT Clostridium botulinum and Bacillus anthracis produce potent toxins that cause severe disease in humans. New and improved vaccines are needed for both of these pathogens. For mucosal vaccine delivery using lactic acid bacteria, chromosomal expression of antigens is preferred over plasmid-based expression systems, as chromosomal expression circumvents plasmid instability and the need for antibiotic pressure. In this study, we constructed three strains of Lactobacillus acidophilus NCFM expressing from the chromosome (i) the nontoxic host receptor-binding domain of the heavy chain of Clostridium botulinum serotype A neurotoxin (BoNT/A-Hc), (ii) the anthrax protective antigen (PA), and (iii) both the BoNT/A-Hc and the PA. The BoNT/A-Hc vaccine cassette was engineered to contain the signal peptide from the S-layer protein A from L. acidophilus and a dendritic-cell-targeting peptide. A chromosomal region downstream of lba0889 carrying a highly expressed enolase gene was selected for insertion of the vaccine cassettes. Western blot analysis confirmed the heterologous expression of the two antigens from plasmid and chromosome locations. Stability assays demonstrated loss of the vaccine cassettes from expression plasmids without antibiotic maintenance. RNA sequencing showed high expression of each antigen and that insertion of the vaccine cassettes had little to no effect on the transcription of other genes in the chromosome. This study demonstrated that chromosomal integrative recombinant strains are promising vaccine delivery vehicles when targeted into high-expression chromosomal regions. Levels of expression match high-copy-number plasmids and eliminate the requirement for antibiotic selective maintenance of recombinant plasmids. IMPORTANCE Clostridium botulinum and Bacillus anthracis produce potent neurotoxins that pose a biochemical warfare concern; therefore, effective vaccines against these bacteria are required. Chromosomal expression of antigens is

  1. Sensing the deadliest toxin: technologies for botulinum neurotoxin detection.

    Science.gov (United States)

    Capek, Petr; Dickerson, Tobin J

    2010-01-01

    Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples.

  2. Cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A: results from the botulinum toxin for the upper limb after stroke (BoTULS) trial.

    Science.gov (United States)

    Shackley, Phil; Shaw, Lisa; Price, Christopher; van Wijck, Frederike; Barnes, Michael; Graham, Laura; Ford, Gary A; Steen, Nick; Rodgers, Helen

    2012-12-01

    Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY) gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER) of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

  3. Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS Trial

    Directory of Open Access Journals (Sweden)

    Nick Steen

    2012-11-01

    Full Text Available Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

  4. Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity.

    Directory of Open Access Journals (Sweden)

    Yongfeng Fan

    Full Text Available The paralytic disease botulism is caused by botulinum neurotoxins (BoNT, multi-domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but cannot enter, bind to or neutralize BoNT that has already entered the neuron. The light chain endopeptidase domain (LC of BoNT serotype A (BoNT/A was targeted for generation of monoclonal antibodies (mAbs that could reverse paralysis resulting from intoxication by BoNT/A. Single-chain variable fragment (scFv libraries from immunized humans and mice were displayed on the surface of yeast, and 19 BoNT/A LC-specific mAbs were isolated by using fluorescence-activated cell sorting (FACS. Affinities of the mAbs for BoNT/A LC ranged from a KD value of 9.0×10-11 M to 3.53×10-8 M (mean KD 5.38×10-9 M and median KD 1.53×10-9 M, as determined by flow cytometry analysis. Eleven mAbs inhibited BoNT/A LC catalytic activity with IC50 values ranging from 8.3 ~73×10-9 M. The fine epitopes of selected mAbs were also mapped by alanine-scanning mutagenesis, revealing that the inhibitory mAbs bound the α-exosite region remote from the BoNT/A LC catalytic center. The results provide mAbs that could prove useful for intracellular reversal of paralysis post-intoxication and further define epitopes that could be targeted by small molecule inhibitors.

  5. Botulinum Toxin for Neuropathic Pain: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Hyun-Mi Oh

    2015-08-01

    Full Text Available Botulinum neurotoxin (BoNT, derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post-traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome.

  6. Botulinum Toxin A for Bladder Pain Syndrome/Interstitial Cystitis

    Directory of Open Access Journals (Sweden)

    Bin Chiu

    2016-07-01

    Full Text Available Botulinum neurotoxin A (BoNT-A, derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC. However, in the field of urology, chronic bladder or pelvic pain is often difficult to eradicate by oral medications or bladder instillation therapy. We are looking for new treatment modality to improve bladder pain or associated urinary symptoms such as frequency and urgency for patients with BPS/IC. Recent studies investigating the mechanism of the antinociceptive effects of BoNT A suggest that it can inhibit the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. In this review, we will examine the evidence supporting the use of BoNTs in bladder pain from basic science models and review the clinical studies on therapeutic applications of BoNT for BPS/IC.

  7. Characterization of Clostridium sp. RKD producing botulinum-like neurotoxin.

    Science.gov (United States)

    Dixit, Aparna; Dhaked, Ram Kumar; Alam, Syed Imteyaz; Singh, Lokendra

    2005-07-01

    A Gram positive, motile, rod-shaped, strictly anaerobic bacterium isolated from intestine of decaying fish was identified as Clostridium sp. RKD and produced a botulinum type B-like neurotoxin as suggested by mouse bioassay and protection with anti botulinum antibodies. The neurotoxicity was functionally characterized by the phrenic nerve hemi-diaphragm assay. Phylogenetic analysis based on 16S rDNA sequence, placed it at a different position from the reported strains of Clostridium botulinum. The strain exhibited differences from both Clostridium botulinum and Clostridium tetani with respect to morphological, biochemical and chemotaxonomic characteristics. Botulinum group specific and serotype specific primers amplified the DNA fragments of 260 and 727 bp, respectively, indicating presence of botulinum type 'B' toxin gene. Sequence of nearly 700 bp amplified using primers specific for botulinum neurotoxin type B gene, did not show any significant match in the database when subjected to BLAST search.

  8. Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study

    Science.gov (United States)

    Al-Wayli, Hessa

    2017-01-01

    Background To evaluate the role of botulinum toxin type A (BTX-A) in the treatment of pain associated with nocturnal bruxism. Material and Methods Fifty subjects reporting nocturnal bruxism were recruited for a randomized clinical trial. Twenty five bruxers were injected with botulinum toxin in both masseters, and twenty five were treated with traditional methods of treating bruxism. Patients were evaluated at 3rd week, 2nd and 6th month and one year after injection and then used to calculate bruxism events. Bruxism symptoms were investigated using questionnaires. Results Mean pain score due to Bruxism events in the masseter muscle decreased significantly in the botulinum toxin injection group A (P =0.000, highly significant). However, in the conventional treatment group, mean pain score does not show improvement with time (p>0.05). Conclusions Our results suggest that botulinum toxin injection reduced the mean pain score and number of bruxism events, most likely by decreasing the muscle activity of masseter rather than affecting the central nervous system. Key words:Temporomandibular pain, nocturnal bruxism, botulinum toxin.

  9. Botulinum Toxin for the Treatment of Myofascial Pain Syndromes Involving the Neck and Back: A Review from a Clinical Perspective

    Directory of Open Access Journals (Sweden)

    José M. Climent

    2013-01-01

    Full Text Available Introduction. Botulinum toxin inhibits acetylcholine (ACh release and probably blocks some nociceptive neurotransmitters. It has been suggested that the development of myofascial trigger points (MTrP is related to an excess release of ACh to increase the number of sensitized nociceptors. Although the use of botulinum toxin to treat myofascial pain syndrome (MPS has been investigated in many clinical trials, the results are contradictory. The objective of this paper is to identify sources of variability that could explain these differences in the results. Material and Methods. We performed a content analysis of the clinical trials and systematic reviews of MPS. Results and Discussion. Sources of differences in studies were found in the diagnostic and selection criteria, the muscles injected, the injection technique, the number of trigger points injected, the dosage of botulinum toxin used, treatments for control group, outcome measures, and duration of followup. The contradictory results regarding the efficacy of botulinum toxin A in MPS associated with neck and back pain do not allow this treatment to be recommended or rejected. There is evidence that botulinum toxin could be useful in specific myofascial regions such as piriformis syndrome. It could also be useful in patients with refractory MPS that has not responded to other myofascial injection therapies.

  10. Botulinum Toxin for the Treatment of Myofascial Pain Syndromes Involving the Neck and Back: A Review from a Clinical Perspective

    Science.gov (United States)

    Climent, José M.; Fenollosa, Pedro; Martin-del-Rosario, Francisco

    2013-01-01

    Introduction. Botulinum toxin inhibits acetylcholine (ACh) release and probably blocks some nociceptive neurotransmitters. It has been suggested that the development of myofascial trigger points (MTrP) is related to an excess release of ACh to increase the number of sensitized nociceptors. Although the use of botulinum toxin to treat myofascial pain syndrome (MPS) has been investigated in many clinical trials, the results are contradictory. The objective of this paper is to identify sources of variability that could explain these differences in the results. Material and Methods. We performed a content analysis of the clinical trials and systematic reviews of MPS. Results and Discussion. Sources of differences in studies were found in the diagnostic and selection criteria, the muscles injected, the injection technique, the number of trigger points injected, the dosage of botulinum toxin used, treatments for control group, outcome measures, and duration of followup. The contradictory results regarding the efficacy of botulinum toxin A in MPS associated with neck and back pain do not allow this treatment to be recommended or rejected. There is evidence that botulinum toxin could be useful in specific myofascial regions such as piriformis syndrome. It could also be useful in patients with refractory MPS that has not responded to other myofascial injection therapies. PMID:23533477

  11. Botulinum toxin for the treatment of myofascial pain syndromes involving the neck and back: a review from a clinical perspective.

    Science.gov (United States)

    Climent, José M; Kuan, Ta-Shen; Fenollosa, Pedro; Martin-Del-Rosario, Francisco

    2013-01-01

    Introduction. Botulinum toxin inhibits acetylcholine (ACh) release and probably blocks some nociceptive neurotransmitters. It has been suggested that the development of myofascial trigger points (MTrP) is related to an excess release of ACh to increase the number of sensitized nociceptors. Although the use of botulinum toxin to treat myofascial pain syndrome (MPS) has been investigated in many clinical trials, the results are contradictory. The objective of this paper is to identify sources of variability that could explain these differences in the results. Material and Methods. We performed a content analysis of the clinical trials and systematic reviews of MPS. Results and Discussion. Sources of differences in studies were found in the diagnostic and selection criteria, the muscles injected, the injection technique, the number of trigger points injected, the dosage of botulinum toxin used, treatments for control group, outcome measures, and duration of followup. The contradictory results regarding the efficacy of botulinum toxin A in MPS associated with neck and back pain do not allow this treatment to be recommended or rejected. There is evidence that botulinum toxin could be useful in specific myofascial regions such as piriformis syndrome. It could also be useful in patients with refractory MPS that has not responded to other myofascial injection therapies.

  12. Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a non-randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ulusoy Nefise B

    2004-03-01

    Full Text Available Abstract Background Although lateral internal sphincterotomy is the gold-standard treatment for chronic anal fissure, intrasphincteric injection of botulinum toxin seems to be a reliable new option. The aim of this non-randomized study is to compare the effect of lateral internal sphincterotomy and botulinum toxin injection treatments on the outcome and reduction of anal sphincter pressures in patients with chronic anal fissure. Methods Patients with chronic anal fissure were treated with either botulinum toxin injection or lateral internal sphincterotomy by their own choice. Maximal resting pressure and maximal squeeze pressure measurements were performed before and 2 weeks after treatments by anal manometry. Patients were followed for fissure relapse during 14 months. Results Twenty-one consecutive outpatients with posterior chronic anal fissure were enrolled. Eleven patients underwent surgery and ten patients received botulinum toxin injection treatment. Before the treatment, anal pressures were found to be similar in both groups. After the treatment, the maximal resting pressures were reduced from 104 ± 22 mmHg to 86 ± 15 mmHg in the surgery group (p 0.05 in the surgery group, and from 117 ± 62 mmHg to 76 ± 34 (p 0.05. There were no relapses during the 14 months of follow up. Conclusion Lateral internal sphincterotomy and botulinum toxin injection treatments both seem to be equally effective in the treatment of chronic anal fissure.

  13. Treatment of inferior lateral pterygoid muscle dystonia with zolpidem tartrate, botulinum toxin injections, and physical self-regulation procedures: a case report.

    Science.gov (United States)

    Vazquez-Delgado, Eduardo; Okeson, Jeffrey P

    2004-10-01

    The following case report depicts the management of a patient suffering with a jaw opening oromandibular dystonia using a combination of botulinum toxin injections, zolpidem, and relaxation procedures. Eventually the botulinum toxin injections were eliminated, and the patient was maintained with only zolpidem and relaxation procedures.

  14. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin

    Science.gov (United States)

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H.; Lokkegaard, Annemette; Marti, Maria J.; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D.; Zoons, Evelien; Ferreira, Joaquim J.; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A. J.

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored. PMID:28286494

  15. Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

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    Svetel Marina

    2007-01-01

    Full Text Available Background/Aim. Spasmodic dysphonia (DS is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80−100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. Methods. The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12−16 units each. In our study we applied indirect technique originally developed by Hočevar and Pirtošek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. Results. The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index − (VHI that was rated as rather significant one (t = 3.562; p = 0.006. Conclusion. Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.

  16. Adeno-Associated Virus Transfer of a Gene Encoding SNAP-25 Resistant to Botulinum Toxin A Attenuates Neuromuscular Paralysis Associated with Botulism

    Science.gov (United States)

    2008-04-02

    refinement of the technology for application to genetic disorders of motor neurons. 15. SUBJECT TERMS Clostridium botulinum, neurotoxiin, serotype...peripherally transported transgenic protein successfully substituted for native cleavage-susceptible S25, as demonstrated by enhanced retention of nerve

  17. The susceptibility of the mallard duck (Anas platyrhynchos) to Clostridium botulinum C2 toxin

    Science.gov (United States)

    Jensen, W.I.; Duncan, R.M.

    1980-01-01

    Most strains of Clostridium botulinum type C, after having lost their capacity to produce their dominant toxin (C1) as a result of being "cured" of their prophages, continue to produce C2, a trypsin-activable toxin reported by other investigators. While of relatively low toxicity when administered perorally to the adult mallard duck (Anas platyrhynchos), it was highly toxic when given parenterally. By the intravenous route, for example, it was more than 1,000 times as toxic as C1 toxin by the same route, when compared on the basis of mouse intraperitoneal toxicity. The cause of death in every instance was massive pulmonary edema and hemorrhage rather than the respiratory paralysis that occurs in C1 intoxication.

  18. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production

    Science.gov (United States)

    Walshaw, John; Peck, Michael W.; Barker, Gary C.

    2016-01-01

    Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. PMID:27855161

  19. The Action of Botulinum Toxin at the Neuromuscular Junction

    Science.gov (United States)

    1980-12-22

    6. PERFORMING ORG. REPORT NUMBER AUTHOR(&) 8. CONTRACT OR GRANT NUMBER(&) SELLIN,/Lawrence C,’c ISM PERFORMING ORGANIZATION NAME AND ADDRESS 10...one quantum. however, end-plate potentials remained subthreshold and did not produce a muscle contraction upon nerve stimulation. Low frequency (0.5 Hz...muscle fibers -"_re not significantly affected by the toxin. It is interesting to note that, although fast- twitch and slow-twitch mucles were

  20. Bruxism after brain injury: successful treatment with botulinum toxin-A.

    Science.gov (United States)

    Ivanhoe, C B; Lai, J M; Francisco, G E

    1997-11-01

    Bruxism, the rhythmic grinding of teeth--usually during sleep--is not an infrequent complication of traumatic brain injury. Its prevalence in the general population is 21%, but its incidence after brain injury is unknown. Untreated, bruxism causes masseter hypertrophy, headache, temporomandibular joint destruction, and total dental wear. We report a case of complete resolution of postanoxic bruxism after treatment with botulinum toxin-A (BTX-A). The patient was a 28-year-old man with no history of bruxism who sustained an anoxic brain injury secondary to cardiac arrest of unknown etiology. On admission to our rehabilitation unit 2 months after the injury, the patient presented with severe bruxism and heavy dental wear. The patient was injected with a total of 200 units of BTX-A to each masseter and temporalis. There was total resolution of bruxism 2 days after injection, with no complications. On follow-up 3 months after injection, the patient remained free of bruxism. We propose that botulinum toxin be considered as a treatment for bruxism secondary to anoxic brain injury. Further studies regarding muscle selection and medication dosage are warranted to elucidate the toxin's efficacy in this condition.

  1. The Antigenicity Analysis of Botulinum Toxin of Clostridium botulinum Type C%C型肉毒梭菌肉毒毒素的抗原性分析

    Institute of Scientific and Technical Information of China (English)

    王娟娟; 刘书东; 李剑; 刘志龙; 陈根元; 曹玉华; 李莲瑞

    2012-01-01

    [目的]通过对分离纯化的C型肉毒毒素抗原性分析,提供快速鉴定动物因C型肉毒梭菌中毒的理论基础.[方法]对分离纯化的C型肉毒梭菌的肉毒毒素灭活后通过SDS - PAGE测定浓度,确定浓度后与弗氏佐剂乳化后免疫家兔,免疫结束后采家兔血液并分离血清.[结果]将不同稀释倍数的肉毒毒素经SDS -PAGE电泳分离后,转移至HybondNC膜,家兔三免后提取的血清作为一抗,用二抗进行Western blotting检测,大约在98.0和53.0 kDa处出现特异反应带;抗原与抗体在琼脂凝胶上结合时,会形成清晰的沉淀带.[结论]分离纯化的C型肉毒毒素,经免疫后家兔可见:C型肉毒毒素具有免疫原性和反应原性,抗体的效价为1∶8.%[Objective ] The study aims to provide the theoretical basis for quick identification of Clostridium botulinum type C through the separation and purification of type C botulinum toxin antigenic analysis. [ Method ] The experiments were carried out by separating and purifyinng Clostridium botulinum type C in the blood collected from Freunds adjuvant emulsified rabbit and the botulinum toxin was inactivated to determine the concentration by SDS - PAGE. The rabbit blood was collected after immunization and the serum was separated. [ Result ] Different dilutions of botulinum toxin were separated by SDS - PAGE electrophoresis, transferred to HybondNC film, and the three free extracted serum from rabbits was used as primary antibody. The secondary antibody was used for Western blotting analysis. At approximately 98.0 and 53.0 kDa, specific reaction zone appeared; antigens and antibodies in agar gel when combined will form a clear precipitation band. [Conclusion]The immunized rabbits, whose botulinum toxin type C was separated and purified by us, are still there. C botulinum toxin has the characteristics of immunogenicity and reactogenicity, and its antibody ti-ter is 1=8.

  2. Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Zhuji; Chen, Chen; Barbieri, Joseph T.; Kim, Jung-Ja P.; Baldwin, Michael R.; (MCW)

    2010-02-22

    Botulinum neurotoxin causes rapid flaccid paralysis through the inhibition of acetylcholine release at the neuromuscular junction. The seven BoNT serotypes (A-G) have been proposed to bind motor neurons via ganglioside-protein dual receptors. To date, the structure-function properties of BoNT/F host receptor interactions have not been resolved. Here, we report the crystal structures of the receptor binding domains (HCR) of BoNT/A and BoNT/F and the characterization of the dual receptors for BoNT/F. The overall polypeptide fold of HCR/A is essentially identical to the receptor binding domain of the BoNT/A holotoxin, and the structure of HCR/F is very similar to that of HCR/A, except for two regions implicated in neuronal binding. Solid phase array analysis identified two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core. Using affinity chromatography, HCR/F bound native synaptic vesicle glycoproteins as part of a protein complex. Deglycosylation of glycoproteins using {alpha}(1-3,4)-fucosidase, endo-{beta}-galactosidase, and PNGase F disrupted the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, was unaffected. These data indicate that the HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2. The interaction of HCR/F with gangliosides was also investigated. HCR/F bound specifically to gangliosides that contain {alpha}2,3-linked sialic acid on the terminal galactose of a neutral saccharide core (binding order GT1b = GD1a GM3; no binding to GD1b and GM1a). Mutations within the putative ganglioside binding pocket of HCR/F decreased binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons. Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons.

  3. Botulinum Toxin in the Treatment of Pediatric Upper Limb Spasticity

    Science.gov (United States)

    Schwabe, Aloysia L.

    2016-01-01

    Botulinum neurotoxin (BoNT) is one of the mainstays in the treatment of pediatric spasticity and dystonia. When considering initiation of BoNT treatment for spasticity, treatment goals and responses to prior conservative measures such as passive range of motion exercises, splinting, and other medication trials should be reviewed. As a general rule, children should be engaged in therapy services around the time of the injections and have a robust home program in place. When managing spasticity in children with BoNT injections, the practitioner should be well versed in functional anatomy with specialized training in injection techniques. Localization techniques in addition to anatomical landmarks are recommended for improved efficacy and include limited electromyography, electrical stimulation, and/or ultrasound guidance. A follow-up visit for the purpose of reassessment during the peak effect of the drug is advised. It is known that BoNT is effective at reducing spasticity and improving range of motion, but it remains to be determined to what degree this translates into improved function, activity, and participation. PMID:26869860

  4. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat

    DEFF Research Database (Denmark)

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob;

    2016-01-01

    and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex mediated torque was normalized to the maximal muscle force (Mmax) evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused...... severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished, but not to the same extent as Mmax at 2 and 4 weeks, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 week, but increased...... that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures....

  5. Injection of Botulinum Toxin a to Upper Esophageal Sphincter for Oropharyngeal Dysphagia in Two Patients with Inclusion Body Myositis

    Directory of Open Access Journals (Sweden)

    Louis WC Liu

    2004-01-01

    Full Text Available Inclusion body myositis (IBM is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles. Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia. This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients.

  6. Off Label Use of Botulinum Toxin in Children under Two Years of Age: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Claudia Druschel

    2013-01-01

    Full Text Available The treatment of children with cerebral palsy with Botulinum Toxin is considered safe and effective, but is only approved for children older than two years of age. The effect of BoNT-A injection on juvenile skeletal muscle especially on neuromuscular junction density, distribution and morphology is poorly delineated and concerns of irreversible damage to the motor endplates especially in young children exist. In contrast, earlier treatment could be appropriate to improve the attainment of motor milestones and general motor development. This review systematically analyzes the evidence regarding this hypothesis. A database search, including PubMed and Medline databases, was performed and all randomized controlled trials (RCTs comparing the efficacy of Botulinum Toxin in children younger than two years were identified. Two authors independently extracted the data and the methods of all identified trials were assessed. Three RCTs met the inclusion criteria. The results of the analysis revealed an improvement in spasticity of the upper and lower extremities as well as in the range of motion in the joints of the lower limbs. However, evidence of an improvement of general motor development could not be found, as the assessment of this area was not completely specified for this patient group. Based on available evidence it can not be concluded that Botulinum Toxin treatment in children younger than two years improves the achievement of motor milestones. However, there is evidence for the reduction of spasticity, avoiding contractures and delaying surgery. Due to some limitations, the results of this review should be cautiously interpreted. More studies, long-term follow up independent high-quality RCTs with effectiveness analyses are needed.

  7. Neurophysiological changes induced by the botulinum toxin type A injection in children with cerebral palsy.

    Science.gov (United States)

    Frascarelli, Flaminia; Di Rosa, Giuseppe; Bisozzi, Eleonora; Castelli, Enrico; Santilli, Valter

    2011-01-01

    In the last few years botulinum toxin type A (BTX-A) has been widely used in the management of spasticity in children with cerebral palsy in order to reduce hypertonicity and improve functional outcomes enhancing motor skill development. The botulinum toxin injection seems to interact with intrafusal and extrafusal fibers producing a reduction of hypertone both through synaptic blockade and inhibition of stretch reflex loop and these changes may influence not only the spinal cord but also the central nervous system (CNS). The purpose of our study was to determine the neurophysiological changes induced by the BTX-A through an evaluation of cortical somatosensory Evoked Potential (SEP) and Soleus H wave, that is the index of excitability of stretch reflex loop. Eighteen children with Cerebral Palsy (CP), aged between 5 and 12, were recruited at Children's Hospital "Bambino Gesù" of Rome. All children were evaluated with appropriate clinical scales before and 1 month after the BTX-A injection. Neurophysiological measurements were performed before, and 1 month after botulinum toxin injection through lower limb SEPs, M-wave and Soleus H wave recording. After the injection the results showed a statistically significant improvement both of clinical scales and the neurophysiological variables. These findings suggest that spasticity itself can be considered as a factor affecting the cortical SEPs. And even though it seems that BTX-A does not have any direct central effect on sensory pathways we suppose an indirect mechanism on modulation of afferent fibers Ia due to the modification induced by BTX-A to central loop reflex.

  8. Comparison of pneumatic dilation with pneumatic dilation plus botulinum toxin for treatment of achalasia.

    Science.gov (United States)

    Bakhshipour, Alireza; Rabbani, Romina; Shirani, Shapoor; Soleimani, Hosein A S L; Mikaeli, Javad

    2010-01-01

    Among the therapeutic options for achalasia are pneumatic dilatation (PD), an appropriate long-term therapy, and botulinum toxin injection (BT) that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation) in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty-four patients with documented primary achalasia that had low response to two times PD (pneumatic dilation (n=18) or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16), PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score > or = 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7), 87.5% vs. 61.1% (P = 0.59) and 87.5% vs. 55.5% (P = 0.53) at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

  9. Comparison of Pneumatic Dilation with Pneumatic Dilation Plus Botulinum Toxin for Treatment of Achalasia

    Directory of Open Access Journals (Sweden)

    Alireza Bakhshipour

    2010-03-01

    Full Text Available Among the therapeutic options for achalasia are pneumatic dilatation (PD, an appropriate long-term therapy, and botulinum toxin injection (BT that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty- four patients with documented primary achalasia that had low response to two times PD (<50% decrease in symptom score and barium height at 5 minute in timed esophagogram after 3month of late PD were randomized to receive pneumatic dilation (n=18 or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16, PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score ≥ 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7, 87.5% vs. 61.1% (P = 0.59 and 87.5% vs. 55.5% (P = 0.53 at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P < 0.002 and 50.77% in the PD group (P < 0.01 at the end of the first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

  10. Botulinum toxin type A treatment to the upper face: retrospective analysis of daily practice

    Directory of Open Access Journals (Sweden)

    Prager W

    2012-06-01

    Full Text Available Welf Prager,1 Jürgen Huber-Vorländer,2 A Ziah Taufig,3 Matthias Imhof,4 Ulrich Kühne,4 Ruth Weissberg,5 Lars-Peter Kuhr,6 Volker Rippmann,3 Wolfgang G Philipp-Dormston,7 Thomas M Proebstle,8 Claudia Roth,9 Martina Kerscher,10 Claudius Ulmann,11 Tatjana Pavicic121Dermatologikum, Hamburg, 2Fort Malakoff Klinik, Mainz, 3Praxisklinik für Plastische und Ästhetische Chirurgie, Cologne, 4Ästhetische Dermatologie im Medico Palais, Bad Soden, 5Taimerhofstrasse 28, Munich, 6Aqua Medical Spa, Munich; 7Hautzentrum Köln, Cologne, 8Privatklinik Proebstle GmbH, Mannheim, 9Kö-Klinik, Düsseldorf, 10MIN Fakultät/Department Chemie/Kosmetikwissenschaft, Hamburg, 11Kosmas Klinik, Bad Neuenahr-Ahrweiler, 12Klinik und Poliklinik für Dermatologie und Allergologie, Munich, GermanyBackground: Botulinum toxin type A treatment has been used for over 20 years to enhance the appearance of the face. There are several commercially available botulinum toxin type A products used in aesthetic clinical practice. The aim of this retrospective analysis was to compare the clinical efficacy of the most commonly used botulinum toxin type A preparations in daily practice.Methods: Physicians from 21 centers in Germany completed questionnaires based on an inspection of subject files for subjects 18 years of age or over who had received at least two, but not more than three, consecutive treatments with incobotulinumtoxinA, onabotulinumtoxinA, or abobotulinumtoxinA within a 12-month period in the previous 2 years. Data on subject and physician satisfaction, treatment intervals, dosages, and safety were collected from 1256 subjects.Results: There were no statistically significant differences between incobotulinumtoxinA and onabotulinumtoxinA with respect to physician and subject satisfaction, dosages, and adverse effects experienced. Both botulinum toxin type A preparations were well tolerated and effective in the treatment of upper facial lines. Due to low treatment numbers

  11. The Prediction of Botulinum Toxin Structure Based on in Silico and in Vitro Analysis

    Science.gov (United States)

    Suzuki, Tomonori; Miyazaki, Satoru

    2011-01-01

    Many of biological system mediated through protein-protein interactions. Knowledge of protein-protein complex structure is required for understanding the function. The determination of huge size and flexible protein-protein complex structure by experimental studies remains difficult, costly and five-consuming, therefore computational prediction of protein structures by homolog modeling and docking studies is valuable method. In addition, MD simulation is also one of the most powerful methods allowing to see the real dynamics of proteins. Here, we predict protein-protein complex structure of botulinum toxin to analyze its property. These bioinformatics methods are useful to report the relation between the flexibility of backbone structure and the activity.

  12. Adductor laryngeal breathing dystonia in NBIA treated with botulinum toxin-A

    Directory of Open Access Journals (Sweden)

    Vinod Rai

    2013-01-01

    Full Text Available We report a rare case of neurodegeneration with brain iron accumulation (NBIA presented with episodic inspiratory stridor. A 10-year-old boy presented with 3-year history of gradually progressive spastic gait and generalized dystonia (involving all four limbs, neck, jaw, and speech. MRI brain showed "Eye of Tiger" sign. He recently developed severe inspiratory stridor associated with almost gasping respiration. Direct video laryngoscopy showed paradoxical vocal cord closure during inspiration. He was treated with EMG-guided botulinum toxin-A injection given into bilateral thyroarytenoid muscles, resulting in dramatic response with complete disappearance of the stridor within a week. The effect lasted 18 months.

  13. Recurrent TMJ Dislocation Managed with Botulinum Toxin Type A Injections in a Pediatric Patient.

    Science.gov (United States)

    Stark, Thomas R; Perez, Cristina V; Okeson, Jeffrey P

    2015-01-01

    Chronic recurrent temporomandibular joint (TMJ) dislocation is an uncommon condition that is painful and distressing to patients and uniquely challenging for clinicians. Sustained TMJ dislocation is not amenable to manual reduction alone when the etiology is muscular in nature. The purpose of this report was to describe the case of a child presenting with recurring temporomandibular joint dislocation secondary to muscle hyperactivity of unknown etiology that was managed with injections of botulinum toxin type A into the inferior lateral pterygoid muscles. The use of this peripheral antispasmoic neurotoxin is a reasonable, safe, and conservative, palliative treatment option for pediatric patients suffering from chronic recurring TMJ dislocation.

  14. Lower facial remodeling with botulinum toxin type A for the treatment of masseter hypertrophy*

    Science.gov (United States)

    Klein, Fernanda Homem de Mello de Souza; Brenner, Fabiane Mulinari; Sato, Maurício Shigeru; Robert, Fernanda Manfron Batista Rosas; Helmer, Karin Adriane

    2014-01-01

    BACKGROUND Masseter hypertrophy has been treated with botulinum toxin injections because of esthetic complaints especially in Asians. OBJECTIVES The goal of the present study was to evaluate the efficacy of abobotulin toxin use in masseter hipertrophy treatment in Brazilians. METHODS Ten Brazilian female patients with masseter hypertrophy were subjected to injections of 90U of abobotulinum toxin A applied on each side respecting the safety zone stabilished in literature and were followed up for 24 weeks. RESULTS When analyzing the coefficients between measures of middle and lower third of the face obtained from standardized photographs, an increase was observed, with statistical significance at 2 weeks (p=0.005) and 12 weeks (p=0.001). The progression of lower third reduction was 3.94%, 5.26%, 11.99%, and 5.47% (2, 4, 12, and 24 weeks respectively). All patients showed improvement in bruxism after treatment. Observed adverse effects were masticatory fatigue, smile limitation, and smile asymmetry. CONCLUSION The use of abobotulinum toxin A for masseter hypertrophy is effective in Brazilians and reached its maximum effect of facial thinning at 12 weeks. Smile limitation had a higher incidence compared to that reported in the literature and may result from risorius muscle blockage caused by toxin dissemination. Despite its side effects, 80% of the patients would like to repeat the treatment. PMID:25387491

  15. Antioxidant effect of minocycline in gingival epithelium induced by Actinobacillus actinomycetemcomitans serotype B toxin

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    Ernie Maduratna Setiawati

    2009-03-01

    Full Text Available Background: Actinobacillus actinomycetemcomitans (Aa serotype B has been associated with aggressive periodontitis. Gingival epithelial cell is exquisitely sensitive to the toxin and may lead to the epithel protective barrier disruption. Experimental models show that minocycline is not related to it’s antimicrobial effect and protection against neuron cell apoptosis of a number experimental models of brain injury and Parkinson’s disease. Purpose: This study, examined antioxidant effect of minocycline to inhibit apoptosis of gingival epithelium induced crude toxin bacteria Aa serotype B in mice. Methods: Thirty adult mice strain Swiss Webster (balb C were divided randomly into three groups: control group (group A, toxin group (group B and toxin and minocycline group (group C. The mice were taken at 24 hours after application, and then the tissue sections of gingival epithelium were stained with tunnel assay and immunohistochemistry. Result: Treatment with these toxin induced apoptosis of gingival epithelium and was associated with DNA fragmentation and reduced gluthatione (GSH. Minocycline 100 nM significantly increased GSH and reduced apoptosis (p < 0.05. Minocycline provides antioxidant effect against citotoxicity of bacteria Aa serotipe B. Conclusion: Nanomolar concentration of minocycline potential as new therapeutic agent to prevent progressivity of aggressiveness of periodontitis.

  16. [Intravesical botulinum toxin under local anestesia as ambulatory procedure.

    Science.gov (United States)

    Fabuel Alcañiz, José Javier; Martínez Arcos, Laura; Jimenez Cidre, Miguel; Burgos Revilla, Francisco Javier

    2017-09-01

    Bladder hyperactivity is described as the presence of "voiding urgency, generally associated with increased daytime frequency and nocturia, with or without urinary incontinence, in the absence of urinary tract infection or other obvious pathology". Onabotulinum toxin A (BTA) is a recommendable therapeutic option in case of failure, contraindication or refusal of the conservative therapy or other non-pharmacological therapies. The injection of BTA in the detrusor has been performed under local, regional or general anesthesia either in the conventional or major ambulatory surgery operative room or in the cystoscopy room. The objective of this paper is to describe the procedure to perform BTA therapy as an ambulatory operation under intravesical local anesthesia in the cystoscopy room, describing its advantages and limitations.

  17. Combined effects of botulinum toxin and casting treatments on lower limb spasticity after stroke.

    Science.gov (United States)

    Farina, Simona; Migliorini, Claudia; Gandolfi, Marialuisa; Bertolasi, L; Casarotto, Matteo; Manganotti, Paolo; Fiaschi, Antonio; Smania, Nicola

    2008-01-01

    Optimal treatment of spasticity requires a combination of pharmacotherapy and muscle lengthening. We evaluated 13 stroke patients with equinovarus foot randomized to treatment with either botulinum toxin A (BTA) injection plus ankle-foot casting (n=6) or BTA alone (n=7). The tibialis posterior and calf muscles (range of BTA injection: 190 to 320 U) were treated in each patient. Castings were worn at night for four months. Each patient was examined before, and at two and four months after BTA injection using the static and dynamic baropodometric tests, the Modified Ashworth Scale and the 10-meter walking test. At two months, therapeutic effects were observed in both groups. At four months, the study group showed further clinical improvement, while the control group returned to baseline performance. Thus, prolonged stretching of spastic muscles after BTA injection affords long-lasting therapeutic benefit, enhancing the effects of the toxin alone.

  18. [The use of botulinum toxin type a in the acute phase of facial nerve injury after neurosurgical surgery].

    Science.gov (United States)

    Orlova, O R; Akulov, M A; Usachev, D Iu; Taniashin, S V; Zakharov, V O; Saksonova, E V; Mingazova, L R; Surovykh, S V

    2014-01-01

    To evaluate the role of botulinum toxin type A in the acute phase of facial nerve injury after neurosurgical surgery. The study involved 55 patients with acute facial muscle paresis caused by facial nerve injury during surgery on the posterior cranial fossa and cerebello-pontine angle (CPA). The first group consisted of 35 patients (mean age, 48.14±1.26 years) who were administered botulinum toxin type A (xeomin) at a dose of 2-3 U per point in muscles of the intact side of the face. The control group included 20 patients (mean age, 49.85±1.4 years) who underwent standard rehabilitation treatment of this pathology. The treatment efficacy was evaluated using the House-Brackmann Scale, the Yanagihara facial grading system, the Facial Disability Index (FDI), and the Sunnybrook Facial Grading (SFG) Scale. Before treatment, patients of both groups experienced severe dysfunction according to the House-Brackmann Scale. A month after the botulinium toxin type A therapy had been started, a significant improvement in the group of patients who received botulinum toxin was observed at all scales (p<0.05), whereas improvement in the facial nerve function in the second group was observed only by the 3rd month of rehabilitation treatment (p<0.05). The number of synkineses in the patients who did not receive botulinum toxin was 46% higher than that in the first group (p=0.019) one year after the surgery, and it was higher by 91% after 2 years (p<0.001). The use of botulinum toxin type A is reasonable in acute facial nerve injury and should be mandatory in combined therapy of these patients.

  19. Botulinum Toxin Injections for Simple Partial Motor Seizures Associated with Pain

    Directory of Open Access Journals (Sweden)

    Edward C. Mader

    2012-01-01

    Full Text Available Intractable epilepsy with painful partial motor seizures is a relatively rare and difficult disorder to treat. We evaluated the usefulness of botulinum toxin to reduce ictal pain. Two patients received two or four botulinum toxin (BTX injections at one-to-two-month intervals. Patient 1 had painful seizures of the right arm and hand. Patient 2 had painful seizures involving the left foot and leg. Injections were discontinued after improved seizure control following resective surgery. Both patients received significant pain relief from the injections with analgesia lasting at least two months. Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving pain associated with muscle contraction in simple partial motor seizures. Our findings do not support the hypothesis that modulation of motor end-organ feedback affects focal seizure generation. BTX is a safe and reversible treatment that should be considered as part of adjunctive therapy after failure to achieve control of painful partial motor seizures.

  20. Effect of botulinum toxin A and nitroglycerin on random skin flap survival in rats.

    Science.gov (United States)

    Ghanbarzadeh, Kourosh; Tabatabaie, Omid Reza; Salehifar, Ebrahim; Amanlou, Massoud; Khorasani, Ghasemali

    2016-01-01

    A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive. To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model. The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline. BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P<0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45). BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.

  1. Botulinum toxin for chronic anal fissure after biliopancreatic diversion for morbid obesity

    Institute of Scientific and Technical Information of China (English)

    Serafino Vanella; Giuseppe Brisinda; Gaia Marniga; Anna Crocco; Giuseppe Bianco; Giorgio Maria

    2012-01-01

    AIM:To study the effect of botulinum toxin in patients with chronic anal fissure after biliopancreatic diversion (BPD) for severe obesity.METHODS:Fifty-nine symptomatic adults with chronic anal fissure developed after BPD were enrolled in an open label study.The outcome was evaluated clinically and by comparing the pressure of the anal sphincters before and after treatment.All data were analyzed in univariate and multivariate analysis.RESULTS:Two months after treatment,65.4% of the patients had a healing scar.Only one patient had mild incontinence to flatus that lasted 3 wk after treatment,but this disappeared spontaneously.In the multivariate analysis of the data,two registered months after the treatment,sex (P =0.01),baseline resting anal pressure (P =0.02) and resting anal pressure 2 mo after treatment (P < 0.0001) were significantly related to healing rate.CONCLUSION:Botulinum toxin,despite worse results than in non-obese individuals,appears the best alternative to surgery for this group of patients with a high risk of incontinence.

  2. Botulinum Toxin for the Management of Sjögren Syndrome-Associated Recurrent Parotitis.

    Science.gov (United States)

    O'Neil, Luke M; Palme, Carsten E; Riffat, Faruque; Mahant, Neil

    2016-12-01

    Recurrent parotitis is a rare manifestation of Sjögren syndrome. The management of recurrent parotitis is challenging because conservative methods may be of limited efficacy and invasive approaches carry the risk of complications. Botulinum toxin has been shown to reduce salivary flow, and consequently, the results of its use in the management of recurrent parotitis have been encouraging. A 65-year-old female patient with recurrent parotitis due to Sjögren syndrome was referred to us, complaining of weekly bouts of inflammation. She required a course of antibiotics monthly to control bacterial superinfections. We treated her with onabotulinumtoxinA injections into both parotid glands at regular intervals. After her second injection cycle, she denied further inflammatory bouts, has not required antibiotics in more than 36 months, and denied any side effects. Botulinum toxin may be a safe and effective method of treating Sjögren syndrome-associated recurrent parotitis. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Toosendanin interferes with pore formation of botulinum toxin type A in PC12 cell membrane

    Institute of Scientific and Technical Information of China (English)

    Mu-feng LI; Yu-liang SHI

    2006-01-01

    Aim: Botulinum neurotoxins (BoNT) abort the process of neurotransmitter release at presynaptic motor nerve terminals, causing muscle paralysis. The ability of botulinum toxin to produce its effect is dependent on the ability of the light chain to cleave the SNARE proteins associated with transmitter release. Translocation of the light chain protease through the heavy chain-formed channel is a pivotal step in the intoxication process. Toosendanin (TSN), a triterpenoid derivative extracted from a Chinese traditional medicine, has been demonstrated to be an effective cure for experimental botulism. This study was designed to explore the antibotulismic mechanisms of toosendanin. Methods: The inside-out singlechannel recording patch-clamp technique was used to record the BoNT/A-induced currents in the presence and absence of TSN. Results: Channel formation was delayed and the sizes of the channels were reduced in the TSN-treated PC12cell membrane. Conclusion: The antibotulismic effect of TSN might occur via interference with toxin translocation.

  4. Botulinum Toxin as an Alternative to Treat the Spasm of the Near Reflex.

    Science.gov (United States)

    Laria, Carlos; Merino-Suárez, María L; Piñero, David P; Gómez-Hurtado, Arantxa; Pérez-Cambrodí, Rafael J

    2015-01-01

    We describe the case of an eight-year-old girl with complaints of headaches and blurred vision (uncorrected visual acuity: 0.1 decimal) that showed on examination miotic pupils, pseudomyopia, no ocular motility restrictions, and no associated neurological disease. After initial treatment with cyclopentolate for two months, pseudomyopia persisted with an intermittent and variable esotropia. Spectacles of +1 both eyes and atropine 1% one drop daily were then prescribed. The situation improved and remained stable for several weeks, with pseudomyopia and esotropia reappearing later. Finally, botulinum toxin (2.5 iu Botox) was injected in the medial rectus muscle on two occasions and a visual therapy program based on the stimulation of fusional divergence, diplopia, and stereopsis consciousness was recommended. This prescription was combined with the use of atropine during the first few weeks. Orthotropia and corrected distance visual acuity of 1.0 were found three months after treatment. The evolution and clinical results of this case report suggest that botulinum toxin in combination with other therapeutic alternatives may be useful in the treatment of spasm of the near reflex.

  5. Growth of and toxin production by nonproteolytic Clostridium botulinum in cooked puréed vegetables at refrigeration temperatures.

    Science.gov (United States)

    Carlin, F; Peck, M W

    1996-08-01

    Seven strains of nonproteolytic Clostridium botulinum (types B, E, and F) were each inoculated into a range of anaerobic cooked puréed vegetables. After incubation at 10 degrees C for 15 to 60 days, all seven strains formed toxin in mushrooms, five did so in broccoli, four did so in cauliflower, three did so in asparagus, and one did so in kale. Growth kinetics of nonproteolytic C. botulinum type B in cooked mushrooms, cauliflower, and potatoes were determined at 16, 10, 8, and 5 degrees C. Growth and toxin production occurred in cooked cauliflower and mushrooms at all temperatures and in potatoes at 16 and 8 degrees C. The C. botulinum neurotoxin was detected within 3 to 5 days at 16 degrees C, 11 to 13 days at 10 degrees C, 10 to 34 days at 8 degrees C, and 17 to 20 days at 5 degrees C.

  6. Use of immunofluorescence and animal tests to detect growth and toxin production by Clostridum botulinum type E in food.

    Science.gov (United States)

    Midura, T; Taclindo, C; Nygaard, G S; Bodily, H L; Wood, R M

    1968-01-01

    The appearance of Clostridium botulinum type E organisms and of toxin in experimentally inoculated packages of turkey roll was followed to study the time relationship between the presence of vegetative cells and the demonstration of toxin. The presence of vegetative cells was determined by immunofluorescence, and animal tests were used to assay toxin production. Growth initiated from detoxified spores of C. botulinum type E resulted in toxin formation within 24 hr. Presence of fluorescing vegetative cells and of toxin coincided from 1 to 14 days of incubation. Beginning with the next testing date, day 21, differences were observed. Toxin could be detected for a longer time than vegetative cells. Neither toxin nor organisms could be found after 56 days of incubation. The mouse lethal dose tests (MLD per gram of turkey roll) showed fluctuations in the amount of toxin present throughout the period of testing. Maximal amounts of toxin were present during the period when fluorescing organisms were also more numerous. The applications of immunofluorescence in the study and in the diagnosis of botulism is discussed.

  7. Botulinum Toxin as Monotherapy in Symptomatic Trigeminal Neuralgia.

    Science.gov (United States)

    Lunde, Hanne Marie Bøe; Torkildsen, Øivind; Bø, Lars; Bertelsen, Anne Kjørsvik

    2016-06-01

    Trigeminal neuralgia (TN) is one of the most agonizing facial pain disorders that humans endure. Studies on onabotulinum toxin A (BTX-A) treatment for TN are limited, but promising with respect to TN of no identifiable cause. We aimed to investigate the efficiency and safety of BTX-A treatment in a 60-year-old male with diabetes mellitus who in March 2013 presented with TN caused by an exostosis in Meckel's cave. The patient was medically treatment refractory due to insufficient pain relief and adverse events of hyperglycemia, and surgery was declined due to complex anatomy. As a last resort, BTX-A was injected into the pain trigger zones of the trigeminal nerve (V5). Complete analgesia was reported 2 weeks after BTX-A injection. Pain medications were discontinued and laboratory values returned to acceptable levels. Regular BTX-A treatment during the next 28 months showed sustained analgesic effect. BTX-A has an excellent safety profile and may be efficient for patients with symptomatic TN not suited for conventional therapies. © 2016 American Headache Society.

  8. Treatment of severe drooling with botulinum toxin in amyotrophic lateral sclerosis and Parkinson's disease: Efficacy and possible mechanisms

    DEFF Research Database (Denmark)

    Møller, Eigild; Karlsborg, Merete; Jensen, Allan Bardow

    2011-01-01

    Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A)....

  9. Intramural Injection with Botulinum Toxin Type A in Piglet Esophagus. The Influencer on Maximum Load and Elongation

    DEFF Research Database (Denmark)

    Pedersen, Mark Ellebæk; Qvist, Niels; Schrøder, Henrik Daa

    2016-01-01

    Introduction The treatment of esophageal atresia (OA) is challenging. The main goal is to achieve primary anastomosis. We have previously demonstrated in a pig model that intramural injection of botulinum toxin type A (BTX-A) resulted in significant elongation of the esophagus during tensioning u...

  10. Influence of Botulinum Toxin Therapy on Postural Control and Lower Limb Intersegmental Coordination in Children with Spastic Cerebral Palsy

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    Bernard Dan

    2013-01-01

    Full Text Available Botulinum toxin injections may significantly improve lower limb kinematics in gait of children with spastic forms of cerebral palsy. Here we aimed to analyze the effect of lower limb botulinum toxin injections on trunk postural control and lower limb intralimb (intersegmental coordination in children with spastic diplegia or spastic hemiplegia (GMFCS I or II. We recorded tridimensional trunk kinematics and thigh, shank and foot elevation angles in fourteen 3–12 year-old children with spastic diplegia and 14 with spastic hemiplegia while walking either barefoot or with ankle-foot orthoses (AFO before and after botulinum toxin infiltration according to a management protocol. We found significantly greater trunk excursions in the transverse plane (barefoot condition and in the frontal plane (AFO condition. Intralimb coordination showed significant differences only in the barefoot condition, suggesting that reducing the degrees of freedom may limit the emergence of selective coordination. Minimal relative phase analysis showed differences between the groups (diplegia and hemiplegia but there were no significant alterations unless the children wore AFO. We conclude that botulinum toxin injection in lower limb spastic muscles leads to changes in motor planning, including through interference with trunk stability, but a combination of therapies (orthoses and physical therapy is needed in order to learn new motor strategies.

  11. An electromyography guided botulinum toxin injection is effective treatment for objective tinnitus as an office procedure: A case report

    Directory of Open Access Journals (Sweden)

    Emel Çadallı Tatar

    2016-11-01

    Full Text Available Patients with palatal myoclonus may suffer from pulsatile tinnitus stemming from involuntary contractions of tensor veli palatini and levator veli palatini muscles. Botulinum toxin (BTX injection to these muscles is effective in resolving pulsatile tinnitus symptom. We present a case of pulsatile tinnitus who was effectively treated with BTX injection under an electromyography guidance as an office procedure.

  12. Effects of botulinum toxin type A on upper limb function in children with cerebral palsy: a systematic review.

    NARCIS (Netherlands)

    Reeuwijk, A.; Schie, P.E. van; Becher, J.G.; Kwakkel, G.

    2006-01-01

    OBJECTIVE: To evaluate whether botulinum toxin type A injections improve upper limb function in children with cerebral palsy. METHODS: An extensive search was carried out in PUBMED, CINAHL, PICARTA, EMBASE, PEDRO and the Cochrane Controlled Trials Register. Controlled and uncontrolled studies were i

  13. The Effect of Intramural Botulinum Toxin Injections on the Elongation of the Piglet Oesophagus Is Time Dependent

    DEFF Research Database (Denmark)

    Dibbern, Christian Bakholdt; Rose, Morten; Ellebæk, Mark Bremholm

    2017-01-01

    Introduction One in 4,000 infants is born with oesophageal atresia. Approximately 15% of these have a long gap oesophageal atresia, where primary anastomosis is difficult or impossible. Previous studies have shown an effect of intramural botulinum toxin type A (BTX-A) injections on the elongation...

  14. The treatment of drooling by ultrasound-guided intraglandular injections of botulinum toxin type A into the salivary glands.

    NARCIS (Netherlands)

    Jongerius, P.H.; Joosten, F.B.M.; Hoogen, F.J.A. van den; Gabreëls, F.J.M.; Rotteveel, J.J.

    2003-01-01

    OBJECTIVE: The aim of the study was to present the background, procedure, and technique of bilateral ultrasound-guided, single-dose injections of botulinum toxin type A (BTX) into the salivary glands in patients with severe drooling. STUDY DESIGN: Clinical trial. METHODS: Initially, an in vitro stud

  15. Treatment of severe drooling with botulinum toxin in amyotrophic lateral sclerosis and Parkinson's disease: Efficacy and possible mechanisms

    DEFF Research Database (Denmark)

    Møller, Eigild; Karlsborg, Merete; Jensen, Allan Bardow

    2011-01-01

    Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A)....

  16. The Use of Botulinum Toxin for the Treatment of Muscle Spasticity in the First 2 Years of Life

    Science.gov (United States)

    Bakheit, Abdel Magid

    2010-01-01

    Although there are sound theoretical reasons for the use of botulinum toxin (Btx) as early as possible in the management of severe childhood muscle spasticity, the experience with its safety in children younger than 2 years of age is limited and information about its possible effects on the development and maturation of the human motor system…

  17. Botulinum toxin as treatment for focal dystonia : a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharm

  18. [Efficacy of semiconductor laser therapy combined with botulinum toxin A type injection in treatment of temporomandibular disorders].

    Science.gov (United States)

    Jiang, Mei-Yuan; You, Qing-Ling

    2016-12-01

    To observe the efficacy of semiconductor laser therapy in combination with botulinum toxin A type injection in treating temporomandibular disorders and the influence on serum levels of interleukin(IL)-1 and tumor necrosis factor(TNF)-α. Ninety patients with temporomandibular disorders were selected and randomly divided into control group and treatment group with 45 cases in each group. Patients in the control group received semiconductor laser therapy,once per day and 1 course for 1 week. Patients in the treatment group was given semiconductor laser therapy in combination with botulinum toxin A type. 50 U botulinum toxin A type were injected into the masseteric and temporal muscles with 5 injections at different sites in each side. The treatment course of patients was 2 weeks. Fricton scale indexes, pain index, and efficacy were compared between the two groups. Serum levels of IL-1 and TNF-α were detected in both groups. SPSS19.0 software package was used for data analysis. After treatment, PI, DI and CMI in the treatment group were significantly lower than the control group (Ptreatment, VAS score of the treatment group was significantly lower than the control group (Ptreatment group was 93.33%,which was significantly higher than control group (66.67%, Ptreatment group were significantly lower than the control group (Plaser therapy in combination with botulinum toxin A type injection in treating temporomandibular disorders is significant,and may be related to decreased serum levels of IL-1 and TNF-α.

  19. Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design.

    Directory of Open Access Journals (Sweden)

    Yuan-Ping Pang

    Full Text Available Botulinum neurotoxin serotype A (BoNTA causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a K(i (app value of 3.8+/-0.8 microM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC(50 value of 100 microM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 A(2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750-1,500 A(2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a K(i value of 760+/-170 nM using synthesis-based computer-aided molecular design (SBCAMD. This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight

  20. Pentavalent replicon vaccines against botulinum neurotoxins and tetanus toxin using DNA-based Semliki Forest virus replicon vectors

    OpenAIRE

    2014-01-01

    The clostridial neurotoxin (CNT) family includes botulinum neurotoxin (BoNT), serotypes A, B, E, and F of which can cause human botulism, and tetanus neurotoxin (TeNT), which is the causative agent of tetanus. This suggests that the greatest need is for a multivalent or multiagent vaccine that provides protection against all 5 agents. In this study, we investigated the feasibility of generating several pentavalent replicon vaccines that protected mice against BoNTs and TeNT. First, we evaluat...

  1. Food safety objective approach for controlling Clostridium botulinum growth and toxin production in commercially sterile foods.

    Science.gov (United States)

    Anderson, N M; Larkin, J W; Cole, M B; Skinner, G E; Whiting, R C; Gorris, L G M; Rodriguez, A; Buchanan, R; Stewart, C M; Hanlin, J H; Keener, L; Hall, P A

    2011-11-01

    As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (ΣR), and preventing an increase in levels (ΣI) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods.

  2. The Cytolethal Distending Toxin Produced by Nontyphoidal Salmonella Serotypes Javiana, Montevideo, Oranienburg, and Mississippi Induces DNA Damage in a Manner Similar to That of Serotype Typhi

    Science.gov (United States)

    Miller, Rachel A.

    2016-01-01

    ABSTRACT Select nontyphoidal Salmonella enterica (NTS) serotypes were recently found to encode the Salmonella cytolethal distending toxin (S-CDT), an important virulence factor for serotype Typhi, the causative agent of typhoid fever. Using a PCR-based assay, we determined that among 21 NTS serotypes causing the majority of food-borne salmonellosis cases in the United States, genes encoding S-CDT are conserved in isolates representing serotypes Javiana, Montevideo, and Oranienburg but that among serotype Mississippi isolates, the presence of S-CDT-encoding genes is clade associated. HeLa cells infected with representative strains of these S-CDT-positive serotypes had a significantly higher proportion of cells arrested in the G2/M phase than HeLa cells infected with representative strains of S-CDT-negative serotypes Typhimurium, Newport, and Enteritidis. The G2/M cell cycle arrest was dependent on CdtB, the active subunit of S-CDT, as infection with isogenic ΔcdtB mutants abolished their ability to induce a G2/M cell cycle arrest. Infection with S-CDT-encoding serotypes was significantly associated with activation of the host cell’s DNA damage response (DDR), a signaling cascade that is important for detecting and repairing damaged DNA. HeLa cell populations infected with S-CDT-positive serotypes had a significantly higher proportion of cells with DDR protein 53BP1 and γH2AX foci than cells infected with either S-CDT-negative serotypes or isogenic ΔcdtB strains. Intoxication with S-CDT occurred via autocrine and paracrine pathways, as uninfected HeLa cells among populations of infected cells also had an activated DDR. Overall, we show that S-CDT plays a significant role in the cellular outcome of infection with NTS serotypes. PMID:27999166

  3. Computer-aided lead optimization: improved small-molecule inhibitor of the zinc endopeptidase of botulinum neurotoxin serotype A.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available Optimization of a serotype-selective, small-molecule inhibitor of botulinum neurotoxin serotype A (BoNTA endopeptidase is a formidable challenge because the enzyme-substrate interface is unusually large and the endopeptidase itself is a large, zinc-binding protein with a complex fold that is difficult to simulate computationally. We conducted multiple molecular dynamics simulations of the endopeptidase in complex with a previously described inhibitor (K(i (app of 7+/-2.4 microM using the cationic dummy atom approach. Based on our computational results, we hypothesized that introducing a hydroxyl group to the inhibitor could improve its potency. Synthesis and testing of the hydroxyl-containing analog as a BoNTA endopeptidase inhibitor showed a twofold improvement in inhibitory potency (K(i (app of 3.8+/-0.8 microM with a relatively small increase in molecular weight (16 Da. The results offer an improved template for further optimization of BoNTA endopeptidase inhibitors and demonstrate the effectiveness of the cationic dummy atom approach in the design and optimization of zinc protease inhibitors.

  4. Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

    2010-01-01

    The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations.

  5. Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease.

    Science.gov (United States)

    Guidubaldi, Arianna; Fasano, Alfonso; Ialongo, Tamara; Piano, Carla; Pompili, Maurizio; Mascianà, Roberta; Siciliani, Luisa; Sabatelli, Mario; Bentivoglio, Anna Rita

    2011-02-01

    Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT-A) or B (BoNT-B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re-treated with the other serotype. Ultrasound-guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT-A (Dysport) and 2500 U BoNT-B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline. Twenty-seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT-A and BoNT-B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT-B treatments (3.2 ± 3.7 days) compared to BoNT-A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT-A and BoNT-B, respectively (P = NS). The only toxin-related side effect was a change to saliva thickness. Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT-B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT-B treatment. Copyright © 2010 Movement Disorder Society.

  6. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    Science.gov (United States)

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P baclofen with adjuvant botulinum toxin A.

  7. Experience with botulinum toxin therapy for axillary hyperhidrosis and comparison to modelled data for endoscopic thoracic sympathectomy - A quality of life and cost effectiveness analysis.

    Science.gov (United States)

    Gibbons, John P; Nugent, Emmeline; O'Donohoe, Nollaig; Maher, Barry; Egan, Bridget; Feeley, Martin; Tierney, Sean

    2016-10-01

    To estimate cost-effectiveness of botulinum toxin therapy for axillary hyperhidrosis compared to the standard surgical intervention of endoscopic thoracic sympathectomy (ETS). The validated dermatology life quality index questionnaire was given to patients attending for treatment over a 4 month period, to assess their quality of life (QoL) over the preceding week (n = 44). Follow-up was performed 4-6 weeks later by telephone using the same questionnaire to validate the effectiveness of the treatment. The duration of effect of the botulinum toxin treatment was also recorded and this data was used as the basis for cost effectiveness analysis. Using HIPE data, the baseline cost for single intervention using botulinum toxin and ETS was retrieved. Using figures provided by HIPE and expert opinion of the costs of complications, a stochastic model for 10,000 patients was used to evaluate the total costs for ETS including the complications. The results from the QoL analysis show that botulinum toxin therapy is a successful therapy for improvement of symptoms. It was revealed that the mean interval before recurrence of original symptoms after botulinum toxin therapy was 5.6 months. The baseline cost for both treatments are €389 for botulinum toxin and €9389 for uncomplicated ETS. The stochastic model yields a mean cost of €11,390 for ETS including complications. Treatments reached cost equivalence after 13.3 years. However, given the efficacy of the botulinum toxin therapy and the low risk we propose that botulinum toxin therapy for hyperhidrosis should be considered the gold standard. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  8. Altered cortical activation from the hand after facial botulinum toxin treatment.

    Science.gov (United States)

    Haenzi, Sara; Stefanics, Gabor; Lanaras, Tatjana; Calcagni, Maurizio; Ghosh, Arko

    2014-01-01

    Plastic interactions between face and hand cortical tactile circuits occur after severe injuries that affect the hand such as in amputation or spinal cord injury. However, whether loss of facial movements alters the cortical circuits involved in processing tactile inputs from the hand remains unknown. In this prospective observational study we used electroencephalography (EEG) to measure cortical activity evoked by tactile stimulation of the hands before and after botulinum toxin-A-induced facial paralysis. We found a reduction in the tactile event-related potentials (ERPs) 6 weeks after the treatment. This suggests that the limited paralysis of facial muscles induced during cosmetic interventions designed to smooth lines and wrinkles on the face is sufficient to alter the cortical processing of tactile inputs from the hand.

  9. Effects of botulinum toxin type A on healing of injured skeletal muscles

    Directory of Open Access Journals (Sweden)

    Shokravi Ramin

    2007-01-01

    Full Text Available Objectives: (1 Evaluation of microscopic healing of skeletal muscle fibers after injuries, especially the arrangement of new muscle fibers and scar tissue diameter in the injury region. (2 Evaluation of alterations in microscopy of the healing procedure within skeletal muscles after injury following botulinum toxin type A (BTX -A induced muscle immobilization. Materials and Methods: The study was done on 12 white lab rabbits of either sex in a 6-month period. Results: The immobilization of skeletal muscle fibers as a result of the use of BTX-A after injury caused a qualitative increase in fibrous tissue formation in the area of injury, and the BTX-A-induced immobilization for a period of 6 months led to muscle atrophy.

  10. Botulinum toxin: An effective treatment for prosthesis-related hyperhidrosis in patients with traumatic amputations

    Directory of Open Access Journals (Sweden)

    Amanda Lezanski Gujda

    2015-01-01

    Full Text Available Hyperhidrosis-related to prosthesis use in patients who have suffered a traumatic limb amputation presents itself as a barrier to comfort, prosthesis use and overall quality of life. This review intends to encourage dermatologists to consider the use of botulinum toxin A or B for the treatment of hyperhidrosis in the residual limb and may serve as a stimulus for a modern, in-depth, and more comprehensive study. A review of the literature was conducted using the PubMed database, focusing on hyperhidrosis treatment after traumatic limb amputation. Articles discussing hyperhidrosis treatment for amputations secondary to chronic medical conditions were excluded. Seven case studies published over the last 12 years have demonstrated positive outcomes of this treatment strategy. Overall, there is little data examining this topic and current publications focus primarily on small case series. A larger, double-blind, placebo-controlled study would likely benefit veterans, service members, and civilians.

  11. A Case of Painful Hemimasticatory Spasm with Masseter Muscle Hypertrophy Responsive to Botulinum Toxin

    Directory of Open Access Journals (Sweden)

    Jin-Hyuck Kim

    2009-10-01

    Full Text Available Hemimasticatory spasm (HMS is a rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contractions of the unilateral jaw-closing muscles. HMS has been frequently described in association with facial hemiatrophy or localized scleroderma. A 42-year-old female presented with involuntary paroxysmal spasms of the left face, of 6 months duration. Her lower face on the left was markedly hypertrophied without skin lesions. An electrophysiological study indicated that the masseter reflexes and masseteric silent period were attenuated on the affected side. Surface electromyography demonstrated irregular bursts of motor unit potentials at high frequencies up to 200 Hz. Magnetic resonance imaging of the head showed marked hypertrophy of the left masseter muscle. Biopsy of the hypertrophied masseter muscle was normal. Repeated local injections of botulinum toxin noticeably reduced the size of the hypertrophied muscle as well as improved the patient’s symptoms.

  12. Treatment of palmar hyperhidrosis with botulinum toxin type A: 44 months of experience.

    Science.gov (United States)

    Pérez-Bernal, Ana María; Avalos-Peralta, Patricia; Moreno-Ramírez, David; Camacho, Francisco

    2005-09-01

    Palmar hyperhidrosis (PH) can produce social and occupational difficulties and reduce the quality of life of those who suffer from this kind of problem. When dealing with focal hyperhidrosis, the patients' attitudes and their subjective approaches regarding the process may influence the objective evaluation of the disorder. To evaluate, by means of a scale, the subjective improvement of sweat production after treatment with botulinum toxin type A (BTX-A) in a group of patients with severe, invalidating PH. Patients and methods Over a period of 44 months, 69 patients were treated and followed-up, 27 patients had to be treated twice, and 11 patients required a third application; 80-100 U was injected in each palm. Regional nerve block was performed before the procedure. The patients were asked to evaluate their improvement at 1, 3, 6, 9, and 12 months of baseline. At 1 month, 53.6% of the patients reported an excellent improvement. Three months later, results were still excellent in 33.3% of the patients, and acceptable in 29%. From then on there was a statistically significant decrease of BTX-A effectiveness. A second application was carried out at an interval of 7.5 +/- 2.6 months, and a third one at 9 +/- 4.4 months. The following complications could be observed: transitory weakness of hand muscles in 13 patients, wrist pain in 5 patients, and cramps in 1 patient. Botulinum toxin is an effective alternative for the treatment of severe, invalidating PH. The maximum improvement persists up to 3 months; from then on, the effects slowly diminish. In our experience, there were no statistically significant differences with further applications of BTX-A. The patients' subjective assessment can be used to evaluate the sweat production after treatment with BTX-A in those medical centers where a more objective evaluation becomes difficult or impossible.

  13. Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

    Directory of Open Access Journals (Sweden)

    Siro Luvisetto

    2015-09-01

    Full Text Available Botulinum neurotoxin A (BoNT/A is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

  14. Botulinum Toxin Type a as a Therapeutic Agent against Headache and Related Disorders.

    Science.gov (United States)

    Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

    2015-09-01

    Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a "glamour" drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

  15. Experience with different botulinum toxins for the treatment of refractory neurogenic detrusor overactivity

    Directory of Open Access Journals (Sweden)

    Cristiano M. Gomes

    2010-02-01

    Full Text Available PURPOSE: To report our experience with the use of the botulinum toxin-A (BoNT/A formulations Botox® and Prosigne® in the treatment of neurogenic detrusor overactivity (NDO. MATERIALS AND METHODS: At a single institution, 45 consecutive patients with refractory urinary incontinence due to NDO received a single intradetrusor (excluding the trigone treatment with botulinum toxin type A 200 or 300 units. Botox was used for the first 22 patients, and Prosigne for the subsequent 23 patients. Evaluations at baseline and week 12 included assessment of continence and urodynamics. Safety evaluations included monitoring of vital signs, hematuria during the procedure, hospital stay, and spontaneous adverse event reports. RESULTS: A total of 42 patients were evaluated (74% male; mean age, 34.8 years. Significant improvements from baseline in maximum cystometric capacity (MCC, maximum detrusor pressure during bladder contraction, and compliance were observed in both groups (P < 0.05. Improvement in MCC was significantly greater with Botox versus Prosigne (+103.3% vs. +42.2%; P = 0.019. Continence was achieved by week 12 in 16 Botox recipients (76.2% and 10 Prosigne recipients (47.6%; P = 0.057. No severe adverse events were observed. Mild adverse events included 2 cases of transient hematuria on the first postoperative day (no specific treatment required, and 3 cases of afebrile urinary tract infection. CONCLUSIONS: Botox and Prosigne produce distinct effects in patients with NDO, with a greater increase in MCC with Botox. Further evaluation will be required to assess differences between these formulations.

  16. Journal of Tissue Engineering and Reconstructive Surgery%Botulinum Toxin Type A for Lower Facial Rejuvenation

    Institute of Scientific and Technical Information of China (English)

    潘本耘(综述); 王丹茹(审校)

    2016-01-01

    维持下面部的紧致轮廓,是东方女性面部年轻化的重点诉求,多数人倾向于选择微创、低风险的治疗方式。近20年来,无创注射A型肉毒毒素,因相对微创、保守及可逆化而广受青睐,被广泛用于上、中面部的年轻化。而为了追求整体面部轮廓的协调,A型肉毒毒素在下面部年轻化中的应用更是受到广泛关注。我们就A型肉毒毒素在下面部年轻化中的应用进展进行综述。%[Summary] How to keep the firm lower facial contour along with the gradually aging process is the major point that Asian women focus on. They are seeking for an minimally invasive and less risky approach, compared with the traditional surgery. The past two decades has seen the botulinum toxin type A (BTX-A) injection as a relatively noninvasive, conservative, and reversible preferred method for women who seek for beauty. The application of BTX-A in upper and mid face has been widely accepted. The use of BTX-A in the lower face has been attracting more and more attention for harmonious lineament. In this paper, the research progress of Botulinum toxin type A for lower facial rejuvenation was reviewed.

  17. Botulinum toxin A in the treatment of spinal cord injury patients with refractory neurogenic detrusor overactivity

    Directory of Open Access Journals (Sweden)

    Ronaldo A. Alvares

    2010-12-01

    Full Text Available PURPOSE: To evaluate the efficacy of botulinum toxin type A injections in the detrusor muscle in patients with spinal cord injury and urinary incontinence due to detrusor overactivity and refractory to anticholinergic agents. MATERIALS AND METHODS: We prospectively evaluated 22 patients with spinal cord injuries, whose bladders were emptied by intermittent catheterization. All patients had detrusor overactivity and urinary incontinence that proved difficult to treat, despite using high doses of two different anticholinergics. The pre-treatment assessment included a complete urodynamic study and ultrasonography of the kidneys and urinary tract. A one-month follow-up was completed with urodynamic evaluation and the clinical response was evaluated through outpatient consultations and telephone contact. RESULTS: After the procedure, the maximum cystometric capacity and the bladder reflex volume increased, whereas the maximum detrusor pressure and compliance decreased. The mean duration of continence was 7 ± 7 months. In 18 patients (81.8%, it was necessary to administer anticholinergics to achieve continence. Five patients (22.7% had indication of reinjection, and augmentation cystoplasty was indicated in 9 patients (40.9%. CONCLUSION: The use of botulinum toxin in the treatment of neurogenic detrusor overactivity refractory to anticholinergics is an option before more invasive treatments, such as augmentation cystoplasty, are attempted. In our study as well as in the literature, there was improvement in most urodynamic parameters. Overall, 40.9% of patients underwent augmentation cystoplasty and 81.8% of patients needed anticholinergic agents to reach urinary continence. Further studies are necessary to improve the procedure and to achieve better clinical results.

  18. THE PROPERTIES AND LONGITUDINAL EXPERIENCE OF CHINESE TYPE A BOTULINUM TOXIN FOR THE TREATMENT OF FOCAL DYSTONIA AND HEMIFACIAL SPASM

    Institute of Scientific and Technical Information of China (English)

    万新华; 汤晓芙; 王荫椿

    2003-01-01

    Objective. To introduce the properties of Chinese type A botulinum toxin (CBTXA, made by Lanzhou Institute of Biological Products), and its long-term effect for focal dystonia and hemifacial spasm. Method. The purity and recovery of crude and crystalline toxin were tested. Long-term data from 305 patients with hemifacial spasm (HFS), blepharospasm (BS) and cervical dystonia (CD) were evaluated and subgroups of patients received CBTXA injections between 1994 and 2000 in at least six separate treatment sessions, with follow up for 2-8 years. The therapeutic results of the last session CBTXA injections were analyzed in comparison with the first session. Result. CBTXA purity was high[(2.55~2.60)×107D50/mgPr, A260/A280 ≤0.55, high molecular substance accounted for 99.2% of total proteins]. Long term treatment with CBTXA in patients with focal dystonia and HFS was not associated with any decline in benefit, and efficacy may improve slightly with repeat treatments. CBTXA is an excellent long-term treatment of HFS, BS and CD. Conchusion. We conclude that Chinese type A botulinum toxin is of botulinum toxin therapy quality standard according to results obtained from the basic study and long-term clinical applications. The reinjection of CBTXA significantly improves the quality of life of most patients and is a safe, effective and comparatively economical treatment for patients with focal dystonia and HFS.

  19. Tetanus toxin : primary structure, expression in E. coli, and homology with botulinum toxins

    NARCIS (Netherlands)

    Eisel, Ulrich; Jarausch, Wolfgang; Goretzki, Karin; Henschen, Agnes; Engels, Joachim; Weller, Ulrich; Hudel, Martina; Habermann, Ernst; Niemann, Heiner; Rott, R.

    1986-01-01

    A pool of synthetic oligonucleotides was used to identify the gene encoding tetanus toxin on a 75-kbp plasmid from a toxigenic non-sporulating strain of Clostridium tetani. The nucleotide sequence contained a single open reading frame coding for 1315 amino acids corresponding to a polypeptide with a

  20. Tetanus toxin : primary structure, expression in E. coli, and homology with botulinum toxins

    NARCIS (Netherlands)

    Eisel, Ulrich; Jarausch, Wolfgang; Goretzki, Karin; Henschen, Agnes; Engels, Joachim; Weller, Ulrich; Hudel, Martina; Habermann, Ernst; Niemann, Heiner; Rott, R.

    1986-01-01

    A pool of synthetic oligonucleotides was used to identify the gene encoding tetanus toxin on a 75-kbp plasmid from a toxigenic non-sporulating strain of Clostridium tetani. The nucleotide sequence contained a single open reading frame coding for 1315 amino acids corresponding to a polypeptide with a

  1. Botulinum Toxin

    Science.gov (United States)

    2009-01-01

    atypical disease symptoms of nausea, vomiting, diplopia , dysphagia, phagodynia, and instability within 7 h of exposure (Meyer and Eddie, 1951). The man...routes of exposure include, in order of descending frequency: dysphagia, xerostomia, diplopia , dysarthria, fatigue, ptosis of the eyelids

  2. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

    2014-11-01

    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method.

  3. Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial

    OpenAIRE

    Shackley, P; Shaw, L; Price, C.; Wijck, F, van; Barnes, M; Graham, L; Ford, G.A.; Steen, N; Rodgers, H

    2012-01-01

    Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients wi...

  4. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Directory of Open Access Journals (Sweden)

    Michael W. Peck

    2017-01-01

    Full Text Available Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.

  5. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

    Science.gov (United States)

    Peck, Michael W.; Smith, Theresa J.; Anniballi, Fabrizio; Austin, John W.; Bano, Luca; Bradshaw, Marite; Cuervo, Paula; Cheng, Luisa W.; Derman, Yagmur; Dorner, Brigitte G.; Fisher, Audrey; Hill, Karen K.; Kalb, Suzanne R.; Korkeala, Hannu; Lindström, Miia; Lista, Florigio; Lúquez, Carolina; Mazuet, Christelle; Pirazzini, Marco; Popoff, Michel R.; Rossetto, Ornella; Rummel, Andreas; Sesardic, Dorothea; Singh, Bal Ram; Stringer, Sandra C.

    2017-01-01

    Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future. PMID:28106761

  6. Botulinum toxin type-A injection to treat patients with intractable anismus unresponsive to simple biofeedback training.

    Science.gov (United States)

    Zhang, Yong; Wang, Zhen-Ning; He, Lei; Gao, Ge; Zhai, Qing; Yin, Zhi-Tao; Zeng, Xian-Dong

    2014-09-21

    To evaluate the efficacy of botulinum toxin type A injection to the puborectalis and external sphincter muscle in the treatment of patients with anismus unresponsive to simple biofeedback training. This retrospective study included 31 patients suffering from anismus who were unresponsive to simple biofeedback training. Diagnosis was made by anorectal manometry, balloon expulsion test, surface electromyography of the pelvic floor muscle, and defecography. Patients were given botulinum toxin type A (BTX-A) injection and pelvic floor biofeedback training. Follow-up was conducted before the paper was written. Improvement was evaluated using the chronic constipation scoring system. BTX-A injection combined with pelvic floor biofeedback training achieved success in 24 patients, with 23 maintaining persistent satisfaction during a mean period of 8.4 mo. BTX-A injection combined with pelvic floor biofeedback training seems to be successful for intractable anismus.

  7. Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Toshio; Tonozuka, Takashi; Kotani, Mao; Obata, Kanae [Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Oguma, Keiji [Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Nishikawa, Atsushi, E-mail: nishikaw@cc.tuat.ac.jp [Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); CREST, Japan Science and Technology Agency (Japan)

    2007-12-01

    HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.6 Å resolution and the crystal belonged to the hexagonal space group P6{sub 3}. Matthews coefficient and self-rotation function calculations indicate that there is probably one molecule of HA3 in the asymmetric unit. A search for heavy-atom derivatives has been undertaken.

  8. Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial spasm: a nerve conduction study.

    Science.gov (United States)

    Butera, C; Guerriero, R; Amadio, S; Ungaro, D; Tesfaghebriel, H; Bianchi, F; Comi, G; Del Carro, U

    2013-02-01

    Botulinum toxin type-A is currently thought to be effective and safe for hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the neuromuscular junction induces depression of orbicularis oculi muscle compound motor action potential (CMAP). The aim of our study was to evaluate at what extent end-plate functional recovery is possible even in botulinum toxin treatments lasting up to 15 years. We examined 81 outpatients with primary HFS (mean treatment duration = 7.2 ± 4.2 years) who underwent neurophysiologic study, once clinical effect of the previous treatment had vanished. The mean CMAP amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and area of response 2 (R2) of treated orbicularis oculi muscle were measured in comparison to the controlateral side. Mean amplitude of the above mentioned parameters was slightly lower (about 20%; p muscle complex.

  9. Intragastric injection of botulinum toxin for the treatment of obesity. Where are we?

    Institute of Scientific and Technical Information of China (English)

    Diego Garcia-Compean; Hector Maldonado Garza

    2008-01-01

    Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.

  10. Safety of Botulinum Toxin A in Children and Adolescents with Cerebral Palsy in a Pragmatic Setting

    Directory of Open Access Journals (Sweden)

    George Mitsou

    2013-03-01

    Full Text Available This retrospective study aimed to examine the safety of botulinum toxin A (BoNT-A treatment in a paediatric multidisciplinary cerebral palsy clinic. In a sample of 454 patients who had 1515 BoNT-A sessions, data on adverse events were available in 356 patients and 1382 sessions; 51 non-fatal adverse events were reported (3.3% of the total injections number, 8.7% of the patients. On five occasions, the adverse reactions observed in GMFCS V children were attributed to the sedation used (rectal midazolam plus pethidine; buccal midazolam and resulted in prolongation of hospitalization. Of the reactions attributed to the toxin, 23 involved an excessive reduction of the muscle tone either of the injected limb(s or generalized; others included local pain, restlessness, lethargy with pallor, disturbance in swallowing and speech production, seizures, strabismus, excessive sweating, constipation, vomiting, a flu-like syndrome and emerging hypertonus in adjacent muscles. Their incidence was associated with GMFCS level and with the presence of epilepsy (Odds ratio (OR = 2.74 − p = 0.016 and OR = 2.35 − p = 0.046, respectively but not with BoNT-A dose (either total or per kilogram. In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not necessitate major changes in our practice.

  11. Genetic diversity of the flagellin genes of Clostridium botulinum groups I and II.

    Science.gov (United States)

    Woudstra, Cedric; Lambert, Dominic; Anniballi, Fabrizio; De Medici, Dario; Austin, John; Fach, Patrick

    2013-07-01

    Botulinum neurotoxins (BoNTs) are produced by phenotypically and genetically different Clostridium species, including Clostridium botulinum and some strains of Clostridium baratii (serotype F) and Clostridium butyricum (serotype E). BoNT-producing clostridia responsible for human botulism encompass strains of group I (secreting proteases, producing toxin serotype A, B, or F, and growing optimally at 37°C) and group II (nonproteolytic, producing toxin serotype E, B, or F, and growing optimally at 30°C). Here we report the development of real-time PCR assays for genotyping C. botulinum strains of groups I and II based on flaVR (variable region sequence of flaA) sequences and the flaB gene. Real-time PCR typing of regions flaVR1 to flaVR10 and flaB was optimized and validated with 62 historical and Canadian C. botulinum strains that had been previously typed. Analysis of 210 isolates of European origin allowed the identification of four new C. botulinum flaVR types (flaVR11 to flaVR14) and one new flaVR type specific to C. butyricum type E (flaVR15). The genetic diversity of the flaVR among C. botulinum strains investigated in the present study reveals the clustering of flaVR types into 5 major subgroups. Subgroups 1, 3, and 4 contain proteolytic Clostridium botulinum, subgroup 2 is made up of nonproteolytic C. botulinum only, and subgroup 5 is specific to C. butyricum type E. The genetic variability of the flagellin genes carried by C. botulinum and the possible association of flaVR types with certain geographical areas make gene profiling of flaVR and flaB promising in molecular surveillance and epidemiology of C. botulinum.

  12. Comparative study of efficacy and safety of botulinum toxin a injections and subcutaneous curettage in the treatment of axillary hyperhidrosis

    OpenAIRE

    Leelavathy Budamakuntla; Eswari Loganathan; Anju George; B N Revanth; Sankeerth, V; Sacchidananda Aradhya Sarvjnamurthy

    2017-01-01

    Background: Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. Aims and Objectives: The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and...

  13. Antibody-induced secondary treatment failure in a patient treated with botulinum toxin type A for glabellar frown lines

    OpenAIRE

    Stengel G; Bee EK

    2011-01-01

    Gabriele Stengel, Eva Kristina Bee Hautarztpraxis Stengel and Bee, Münster, Germany Abstract: Botulinum toxin type A (BTX-A) preparations are widely used nonsurgical treatments for facial wrinkles. Higher doses of BTX-A are also used for therapeutic purposes in the treatment of conditions involving increased muscle tone, such as cervical dystonia. The phenomenon of antibody-induced treatment failure is well known in the therapeutic setting, but reports are also emerging following co...

  14. Comparative Study of Efficacy and Safety of Botulinum Toxin a Injections and Subcutaneous Curettage in the Treatment of Axillary Hyperhidrosis

    OpenAIRE

    Budamakuntla, Leelavathy; Loganathan, Eswari; George, Anju; Revanth, BN; Sankeerth, V; Sarvjnamurthy, Sacchidananda Aradhya

    2017-01-01

    Background: Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. Aims and Objectives: The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and...

  15. Effect of a clown’s presence at botulinum toxin injections in children: a randomized, prospective study

    Directory of Open Access Journals (Sweden)

    Hansen LK

    2011-09-01

    Full Text Available Lars Kjaersgaard Hansen1, Maria Kibaek1, Torben Martinussen2, Lene Kragh3, Mogens Hejl11Department of Paediatrics, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense; 2Roskilde Hospital, Roskilde; 3Department of Statistics, University of Southern Denmark, Odense, DenmarkBackground: The effect of the presence of a hospital clown during pediatric procedures has rarely been evaluated. In a pediatric ward, botulinum toxin injection is a painful procedure and a stressful experience for the child. We undertook a study of the effect of the presence of a hospital clown on children treated with botulinum toxin in an outpatient setting.Methods: In total, 60 children, the majority of whom had spastic cerebral palsy, were subjected to a total of 121 botulinum toxin treatment sessions. Thirty-two children were being treated for the first time. During a 2-year period, we enrolled 121 treatment sessions prospectively, and the children were randomized to either the presence of a female clown during treatment or to no presence of a clown. The duration of the child's crying during the procedure was used as an indicator of the effect of the presence of a clown.Results: The effect of the clown was significantly related to patient gender. Girls were found to have a significantly shorter period of crying when the clown was present. For children younger than 8 years, the effect on boys was negative. Children treated for the first time did not appear to benefit from the presence of the clown, and showed no difference in effect between genders.Conclusion: No effect of the clown was documented for children being treated for the first time. At repeat treatments, we saw a positive effect of the female clown in relation to girls, and a negative effect on boys younger than 8 years of age.Keywords: clown, injections, pain, botulinum toxin

  16. The use of botulinum toxin injections to manage drooling in amyotrophic lateral sclerosis/motor neurone disease: a systematic review.

    Science.gov (United States)

    Squires, Nina; Humberstone, Miles; Wills, Adrian; Arthur, Antony

    2014-08-01

    Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar weakness including dysphagia. There are no definitive evidence-based treatment guidelines to manage the distressing symptom of drooling. We reviewed the evidence for the effectiveness of botulinum toxin injections to reduce saliva in ALS/MND. The search strategy was conducted in four stages: (1) electronic search of relevant databases, (2) hand searches of all international ALS/MND symposium journals, (3) email request to MND care centres in the UK and Ireland, and (4) hand searching of reference lists. All studies were critically appraised and relevant data extracted. Botulinum toxin type A and type B were analysed separately. Due to heterogeneity, it was not possible to calculate a pooled estimate of effect. Twelve studies met the inclusion criteria (9 for type A and 3 for type B). Only two randomised controlled trials were identified. Study sample sizes were small with a mean of 12.5 subjects. The most frequently reported outcomes were weight of cotton rolls and number of tissues used. All studies claimed the intervention tested was effective, but only seven studies (4 for type A and 3 for type B) reported statistically significant differences. Although there is evidence to suggest that botulinum toxin B can reduce drooling, the evidence base is limited by a lack of randomized controlled trials. Evidence to support the use of botulinum toxin A is weaker. Larger trials will help remove the uncertainty practitioners face in treating this disabling symptom.

  17. Botulinum Toxin Type a Injection, Followed by Home-Based Functional Training for Upper Limb Hemiparesis after Stroke

    Science.gov (United States)

    Takekawa, Toru; Kakuda, Wataru; Taguchi, Kensuke; Ishikawa, Atsushi; Sase, Yousuke; Abo, Masahiro

    2012-01-01

    Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment for limb spasticity after stroke. However, the reduction in the spasticity after BoNT-A injection alone does not ensure an improvement in the active motor function of the affected limb. The aim of this study was to clarify the clinical effects of a BoNT-A injection,…

  18. Botulinum Toxin Type a Injection, Followed by Home-Based Functional Training for Upper Limb Hemiparesis after Stroke

    Science.gov (United States)

    Takekawa, Toru; Kakuda, Wataru; Taguchi, Kensuke; Ishikawa, Atsushi; Sase, Yousuke; Abo, Masahiro

    2012-01-01

    Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment for limb spasticity after stroke. However, the reduction in the spasticity after BoNT-A injection alone does not ensure an improvement in the active motor function of the affected limb. The aim of this study was to clarify the clinical effects of a BoNT-A injection,…

  19. Botulinum toxin uses in strabismus: A review of the injections performed during one year in a general hospital.

    Science.gov (United States)

    Jarrín, E; Arranz Márquez, E; Yebra González, L; García Gil de Bernabé, J

    2016-03-01

    To analyse the indications, dosage and efficacy of botulinum toxin A injection performed in patients in a Strabismus Department. In this prospective study, botulinum toxin A was injected into 28 patients diagnosed with strabismus. Data was obtained from the records of patients that were evaluated during 2013 in the Strabismus Unit of Rey Juan Carlos Hospital (Móstoles, Madrid, Spain) in order to assess the indications and dosage of botulinum toxin A use in strabismus, as well as its clinical effect and differences in paediatric and adult patients. The outcomes in the last visit, at least 14 months after the injections, were analysed. An analysis was performed on the data from 11 children, 6 females (54.5%), and 17 adults, 11 males (64%). The mean age was 4.42±3.48 years and 58.71±18.07 years in the children and adult groups, respectively. The majority of cases in both groups were esotropia (81.8% in children and 47.1% in adults). However the pathologies in the adult group were quite heterogeneous, including 4 patients with exotropia (26.5%), 4 with hypertropia (26.5%), and one with isolated nystagmus (5.9%). The mean number of the botulinum toxin injections in children was 1.45±0.93, although 72.7% received a single injection. In the adult group, the mean number of injections was 3.27±1.41. There was a statistically significant difference between pre- and post-injection in the tropia and phoria measurements in children and adults group (P<.05). In both groups there was a statistically significant improvement in post-injection torticollis when compared with the pre-injection measurement (P<.05). An improvement in the stereoacuity could be detected in 4 children. Two children (18.2%) and 5 adults (29.4%) required subsequent surgical intervention. Eight adult patients (49.1%) complained of diplopia in the primary position, which was resolved in 6 cases with toxin injection, whereas 2 needed surgery for diplopia correction. Botulinum toxin is a very useful tool in

  20. Botulinum toxin type A and B improve quality of life in patients with axillary and palmar hyperhidrosis.

    Science.gov (United States)

    Rosell, Karolina; Hymnelius, Kristina; Swartling, Carl

    2013-05-01

    Hyperhidrosis is a common disorder that may have a severe impact on quality of life. The aim of this study was to investigate the clinical effect of two novel botulinum toxins, Xeomin®, a type A botulinum toxin, and Neuro-bloc®, a type B botulinum toxin, in the treatment of axillary and palmar hyperhidrosis. A total of 84 patients, 58 with axillary and 26 with palmar hyperhidrosis, were included in this open study. Axillae were injected with 107 ± 22 U Xeomin® and palms were injected with 213 ± 19 U Xeomin® and 264 ± 60 U Neurobloc® over the thenar eminences to avoid muscle weakness. At follow-up 3 weeks post-treatment, all patients treated for axillary hyperhidrosis reported satisfaction in self-ranking, evaporation decreased > 40%, and Dermatology Life Quality Index (DLQI) score improved from 12.0 to 1.7 (p 50% and DLQI score improved from 10.3 to 1.2 (p hyperhidrosis and in combination with Neurobloc® on palmar hyperhidrosis. Neurobloc® may be an option for use in the treatment of palmar hyperhidrosis in order to minimize muscular side-effects.

  1. Myofascial pain of the jaw muscles: comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique.

    Science.gov (United States)

    Guarda-Nardini, Luca; Stecco, Antonio; Stecco, Carla; Masiero, Stefano; Manfredini, Daniele

    2012-04-01

    A randomized controlled trial was performed to compare the short-term effectiveness of botulinum toxin injections and physiatric treatment provided by means of Fascial Manipulation techniques in the management of myofascial pain of jaw muscles. Thirty patients with a Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) diagnosis of myofascial pain were randomized to receive either single-session botulinum toxin injections (Group A) or multiple-session Fascial Manipulation (Group B). Maximum pain levels (VAS ratings) and jaw range of motion in millimeters (maximum mouth opening, protrusion, right and left laterotrusion) were assessed at baseline, at the end of treatment, and at a three-month follow-up. Both treatment protocols provided significant improvement over time for pain symptoms. The two treatments seem to be almost equally effective, Fascial Manipulation being slightly superior to reduce subjective pain perception, and botulinum toxin injections being slightly superior to increase jaw range of motion. Differences between the two treatment protocols as to changes in the outcome parameters at the three-months follow-up were not relevant clinically. Findings from the present investigation are in line with literature data supporting the effectiveness of a wide spectrum of conservative treatment approaches to myofascial pain of the jaw muscles. Future studies on larger samples over a longer follow-up span are needed on the way to identify tailored treatment strategies.

  2. Botulinum toxin to improve results in cleft lip repair: a double-blinded, randomized, vehicle-controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Chun-Shin Chang

    Full Text Available BACKGROUND: Most patients with facial scarring would value even a slight improvement in scar quality. Botulinum toxin A is widely used to alleviate facial dynamic rhytides but is also believed to improve scar quality by reducing wound tension during healing. The main objective was to assess the effect of Botulinum toxin on scars resultant from standardized upper lip wounds. METHODS: In this double-blinded, randomized, vehicle-controlled, prospective clinical trial, 60 consecutive consenting adults undergoing cleft lip scar revision (CLSR surgery between July 2010 and March 2012 were randomized to receive botulinum toxin A (n = 30 or vehicle (normal saline; n = 30 injections into the subjacent orbicularis oris muscle immediately after wound closure. Scars were independently assessed at 6-months follow-up in blinded fashion using: Vancouver Scar Scale (VSS, Visual Analogue Scale (VAS and photographic plus ultrasound measurements of scar widths. RESULTS: 58 patients completed the trial. All scar assessment modalities revealed statistically significantly better scars in the experimental than the vehicle-control group. CONCLUSION: Quality of surgical upper lip scars, which are oriented perpendicular to the direction of pull of the underlying orbicularis oris muscle, is significantly improved by its temporary paralysis during wound healing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01429402.

  3. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud's syndrome associated with scleroderma.

    Science.gov (United States)

    Uppal, L; Dhaliwal, K; Butler, P E

    2014-10-01

    Raynaud's syndrome contributes to the pain, paraesthesia, ulceration, and gangrene of scleroderma. Botulinum toxin has been shown to improve digital perfusion in patients with Raynaud's. This is the first study to objectively assess hand function following this treatment in patients with scleroderma. Twenty patients were treated with 100 units of botulinum toxin injected into the hand. An assessment of hand function and symptoms was performed prior to injection and then 8-12 weeks later. The outcomes assessed were change in pain, appearance, cold intolerance, pinch and power grip, ranges of movement, and Disabilities of the Arm, Shoulder and Hand (DASH) score. In total, 80% of patients reported an overall improvement in their symptoms, reduction in pain, and improved DASH score and 65% reported improvement in cold intolerance. Overall, 90% showed an improvement in pinch grip and 65% an improvement in power grip. Objective parameters were statistically significantly improved; however, subjective outcomes only showed a trend. We have found botulinum toxin to be an effective treatment for Raynaud's syndrome secondary to scleroderma. © The Author(s) 2013.

  4. Botulinum toxin type A products are not interchangeable: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Brin MF

    2014-10-01

    Full Text Available Mitchell F Brin,1,2 Charmaine James,3 John Maltman1 1Allergan, Inc., Irvine, CA, USA; 2Department of Neurology, University of California, Irvine, CA, USA; 3Allergan, Marlow, UKAbstract: Botulinum toxin type A (BoNTA products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines.Keywords: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, glabellar lines, non-interchangeability

  5. Botulinum toxin type a for the treatment of spasticity in children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Dimitrijević Lidija

    2007-01-01

    Full Text Available Background/Aim. Cerebral palsy (CP is the most common physical disability in childhood. Children have problems with motor functions as a result of limbs spasticity, which leads to severe contractures and limbs deformity. There is a growing interest in the therapeutic role of botulinum toxin type A (BTA in CP. The aim of this study was to examine the effects of BTA on spasticity, active range of motion and functional motor outcomes in children with CP. Methods. This study included 42 children of both sexes, aged 2−6 years, with spastic CP, divided into two groups: group I (21 child treated with BTA and physical therapy, and group II (21 child treated with physical therapy only. The following parameters were analyzed: spasticity; active range of motion of the hip, knee and ankle, and functional motor outcome. These parameters measurements were carried out four times in both groups: before the treatment, three, eight and 16 weeks after the beginning of the treatment. The obtained results were statistically processed and compared. Results. There was no evidence of any significant difference between the groups before the treatment. After eight weeks there was a remarkable difference concerning spasticity reducing on behalf of the group I (group I - 0.76±0.51 vs. II group - 2.17±0.64; p < 0.0001. There was statistically significant difference concerning active range of motion increasing on behalf of the group I (hip abduction: group I - 44.37±1.130 vs. group II - 32.61±8,070, p < 0,01; knee extension: group I - 0,77±1.820 vs. II group - 14.99±7.610, p < 0.01; dorsiflexion of the foot: group I - 11.50±6.080 vs. group II - 8.98±7.850, p < 0,01. A statistically significant difference was found after 16 weeks in functional motor outcome as well, on behalf of the group I: functional motor abilities level in the group I was 1.86 vs. 2.71 in the group II, p < 0.05. Conclusion. Botulinum toxin type A application leads to an important spasticity

  6. An update on botulinum toxin A injections of trigger points for myofascial pain.

    Science.gov (United States)

    Zhou, Jon Y; Wang, Dajie

    2014-01-01

    Myofascial pain syndrome (MPS) is a common chronic pain condition that is characterized by distinct "trigger points." Despite current treatments with physical therapy, analgesics, anti-depressants and trigger-point injections, myofascial pain remains a challenging chronic pain condition in clinical practice. Botulinum toxin A (BTX-A) can cause prolonged muscle relaxation through inhibition of acetylcholine release. It may offer some advantages over the current treatments for MPS by providing a longer sustained period of pain relief. Despite numerous clinical trials, the efficacy of BTX-A in alleviating MPS is not well-established due to mixed results from recent clinical trials. Active trigger points are associated with referred pain and greatly impact many aspects of activities of daily living, mood, and health status. This review is designed to analyze the clinical trials regarding the efficacy of BTX-A injection of active trigger points as a treatment for MPS. The literature referenced was obtained via a computer search with Google Scholar, Pubmed, Medline and EMbase. Our search terms included "Botulinum toxin," "myofascial pain," "trigger points," "myofascial trigger points," "chronic pain." Additional references were retrieved from the reference list of the reports found via this search. Studies were considered eligible for inclusion if they were double-blinded, randomized, controlled trials evaluating the efficacy of BTX-A injections into trigger points for pain reduction, and if the trigger point selection in the trial included referred pain and/or local twitch response. Open-label studies, case reports, and other non-randomized studies were excluded. Eight trials were found according to the above criteria and are summarized in Table 1. There are well-designed clinical trials to support the efficacy of trigger-point injections with BTX-A for MPS. However, further clinical trials with considerations of minimizing placebo effect, repeated dosing, adequate

  7. Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review.

    Science.gov (United States)

    Oliveira, Ademar Francisco de; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier

    2016-01-01

    Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. RESUMO Esclerose lateral amiotrófica é uma doença neurodegenerativa progressiva e fatal, caracterizada pela degeneração dos neurônios motores, as células do sistema nervoso central que controlam os movimentos voluntários dos músculos. A salivação excessiva (sialorreia) está presente em cerca de 50% dos casos de esclerose lateral amiotrófica. Dessa forma, surgem medidas terapêuticas alternativas como drogas anticolinérgicas e cirurgia, e recentemente, o uso da toxina botulínica, aplicada em um ponto central das glândulas salivares, muitas vezes guiado por ultrassonografia, demostrou resultados positivos. Objetivou-se revisar a literatura no intuito de demonstrar um método alternativo aos tratamentos de sialorreia em pacientes com esclerose lateral amiotrófica. Em estudos recentes, a eficácia do tratamento com toxina botulínica foi confirmada e, mesmo requerendo novas aplicações, os efeitos colaterais são ínfimos. Ela surge então como alternativa não só ao

  8. The effect of laser and botulinum toxin in the treatment of myofascial pain and mouth opening: A randomized clinical trial.

    Science.gov (United States)

    De Carli, Bethânia Molin Giaretta; Magro, Alessandra Kuhn Dall; Souza-Silva, Bianca Núbia; Matos, Felipe de Souza; De Carli, João Paulo; Paranhos, Luiz Renato; Magro, Eduardo Dall

    2016-06-01

    This study conducted a randomized clinical trial in 15 patients, who sought care at the Dental Clinic of the University of Passo Fundo, in order to compare the use of low-level laser and botulinum toxin in the treatment of myofascial pain and whether they alter the mouth opening of patients with temporomandibular disorder. The patients were divided into two groups: the Laser group received low-level GaAlAs laser, 100mW of power at a wavelength of 830nm in continuous light emission; and the Toxin group received 30U of botulinum toxin type A (BTX-A) in the first session, and 15U after fifteen days. The assessments were performed by measuring pain with Visual Analogue Scale (VAS), and mouth opening with a digital caliper. Data were submitted to Student's t test at 5% significance level. Regarding pain symptoms, the results indicate that groups treated with laser and toxin registered 7U in VAS, at day 5 the scores were 4.75 and 4.86U, respectively. The laser worked faster (day 12) at 2.75U, and the group treated with BTX-A registered 2.86U at day 30. Both therapies investigated were effective in reducing pain, but the effect of low-level laser was faster than the use of BTX-A. Both treatments showed no statistically significant improvement in mouth opening.

  9. Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex

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    Tomonori Suzuki

    2017-03-01

    Full Text Available Clostridium botulinum produces the botulinum neurotoxin (BoNT. Previously, we provided evidence for the “building-block” model of botulinum toxin complex (TC. In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA, yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three “arms” of the HA-33/HA-17 trimer (two HA-33 and one HA-17 further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination. In this study, we determined the solution structures for the botulinum TCs using small-angle X-ray scattering (SAXS. The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”, in contrast to the model having three “arms”, as revealed by transmission electron microscopy. SAXS images indicated that one of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. Taken together, these findings regarding the conformational changes in the building-block architecture of TC may explain why only three-arm L-TC exhibited hemagglutination.

  10. Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

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    Bahman Jabbari

    2013-04-01

    Full Text Available Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate are evidence level B (probably effective. Oral agents (oxybutynin and methantheline bromide are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona, while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo in axillary hyperhidrosis (AH, collectively depicting Level A evidence (established for botulinumtoxinA (BoNT-A. In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco no placebo controlled studies exist; thus, efficacy is Level C (possibly effective based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima, one class III study has suggested Level U efficacy (insufficient data. In palmar hyperhidrosis (PH, there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A and no blinded study for A/Inco (level U. For B/Rima the level of evidence is C (possibly effective based on 1 class II study. Botulinum toxins (BoNT provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B; however, data on duration and frequency of application is inconsistent.

  11. Evaluation of voice quality in adductor spasmodic dysphonia before and after botulinum toxin treatment.

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    Langeveld, T P; van Rossum, M; Houtman, E H; Zwinderman, A H; Briaire, J J; Baatenburg de Jong, R J

    2001-07-01

    In this prospective study, the efficacy of botulinum toxin (Botox) injections in patients with adductor spasmodic dysphonia (AdSD) was assessed by 3 different modalities: perceptual and acoustic analyses and subjective self-assessment. This was done by comparing AdSD patients' pretreatment and posttreatment values and comparing these values with those of normal control speakers. In contrast to most other studies, the posttreatment status was defined as the optimal voice quality as judged by the patient. The aim of the study was to assess to what extent Botox injections actually improve voice quality and function. The AdSD subjects rated a significantly improved voice quality and function after Botox treatment. However, the results were never within normal limits. Perceptually, the characteristic and severely impaired AdSD voice improved, but another "type" of pathological voice was detected after Botox treatment. Acoustic analyses demonstrated a significant improvement, as well. Nevertheless, the "optimally" treated AdSD voice still remained significantly deviant as compared to normal voice production. Currently, Botox injection is the therapy of first choice for AdSD. Although significant improvement could be measured in our study perceptually, acoustically, and subjectively, the optimal voice that was achieved never fully matched normal voice quality or function.

  12. Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor spasmodic dysphonia: a prospective study

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    Abiola Jesuloba

    2009-10-01

    Full Text Available Abstract Objectives In this preliminary prospective study, we compared unilateral and bilateral thyroarytenoid muscle injections of Botulinum toxin (Dysport in 31 patients with adductor spasmodic dysphonia, who had undergone more than 5 consecutive Dysport injections (either unilateral or bilateral and had completed 5 concomitant self-rated efficacy and complication scores questionnaires related to the previous injections. We also developed a Neurophysiological Scoring (NPS system which has utility in the treatment administration. Method and materials Data were gathered prospectively on voice improvement (self-rated 6 point scale, length of response and duration of complications (breathiness, cough, dysphagia and total voice loss. Injections were performed under electromyography (EMG guidance. NPS scale was used to describe the EMG response. Dose and unilateral/bilateral injections were determined by clinical judgment based on previous response. Time intervals between injections were patient driven. Results Low dose unilateral Dysport injection was associated with no significant difference in the patient's outcome in terms of duration of action, voice score (VS and complication rate when compared to bilateral injections. Unilateral injections were not associated with any post treatment total voice loss unlike the bilateral injections. Conclusion Unilateral low dose Dysport injections are recommended in the treatment of adductor spasmodic dysphonia.

  13. Intravenous regional anesthesia (Bier's block) for botulinum toxin therapy of palmar hyperhidrosis is safe and effective.

    Science.gov (United States)

    Blaheta, Hans-Juergen; Vollert, Barbara; Zuder, Daniel; Rassner, Gernot

    2002-08-01

    Botulinum toxin type A (BTX-A) has been shown to be highly effective in reducing palmar hyperhidrosis. Since palmar injections is a painful procedure, the use of an anesthesia method is recommended. To assess the efficacy of intravenous regional anesthesia (IVRA) for painless treatment of palmar hyperhidrosis with BTX-A compared to topical application of a local anesthetic agent. Thirty patients with palmar hyperhidrosis were treated with BTX-A injections, using a total dose of 100 U BTX-A for each hand. One palm was pretreated with a topical application of local anesthetizing cream (EMLA cream), while the other palm was anesthetized with IVRA. Sweat secretion was visualized with Minor's test and quantified by corneometer analysis before and after BTX-A therapy. BTX-A therapy was significantly less painful in palms anesthetized with IVRA than in palms pretreated with EMLA cream (P BTX-A injections, corneometer measurements showed that spontaneous sweat production had declined significantly, from 115 +/- 16.25 (left hand) and 114 +/- 17.58 (right hand) before therapy to 81.5 +/- 27.33 (left hand) and 74 +/- 28.08 (right hand) after therapy (P BTX-A treatment for palmar hyperhidrosis. Quantitative analysis with the corneometer showed that BTX-A significantly reduces sweat production. We conclude that IVRA is a suitable method for providing pain relief in the treatment of patients with palmar hyperhidrosis.

  14. Effects of botulinum toxin-a therapy for palmar hyperhidrosis in plantar sweat production.

    Science.gov (United States)

    Gregoriou, Stamatis; Rigopoulos, Dimitris; Makris, Michael; Liakou, Anastasia; Agiosofitou, Efi; Stefanaki, Christina; Kontochristopoulos, George

    2010-04-01

    Patients with focal hyperhidrosis in multiple areas often report improvement of plantar hyperhidrosis after botulinum toxin A (BTX-A) therapy for palmar hyperhidrosis. To assess sweat production from the soles in patients receiving BTX-A treatment for their palmar hyperhidrosis. Thirty-six patients with both palmar and plantar hyperhidrosis received 100 U of BTX-A per palm. Sweat production of palms and soles was assessed using a starch iodine test and gravimetry at baseline and 1, 3, and 8 months after treatment. Patients were subjectively assessed using a percentile scale. All patients had significant improvement in their palmar hyperhidrosis that lasted for 6.2 +/- 1.8 months. Gravimetry revealed marginal improvement of plantar hyperhidrosis in 12 patients (from 39.7 +/- 21.3 to 31.5 +/- 18.0 mg/min; p=.01) and statistically significant worsening in 24 patients (from 71.6 +/- 70.60 to 109.94 +/- 82.93 mg/min, pBTX-A increased plantar sweating in many patients affected by both palmar and plantar hyperhidrosis in the population under study. Regardless, patients reported satisfaction with the results and were willing to repeat treatment.

  15. Botulinum toxin type A treatment for Parkinsonian patients with moderate to severe sialorrhea.

    Science.gov (United States)

    Su, Cheng-San; Lan, Min-Yu; Liu, Jia-Shou; Chang, Chiung-Chih; Lai, Shung-Lon; Wu, Hsiu-Shan; Chen, Shun-Sheng; Chang, Yung-Yee

    2006-09-01

    To investigate the effect of botulinum toxin type A (BTX-A; Botox) in reducing saliva in patients with Parkinsonism. Fifteen patients with clinical diagnosis of idiopathic Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy were enrolled in this open clinical trial. A total of 40-unit dose of Botox was injected into the bilateral parotid and submandibular glands. Objective measuring of saliva production with dental rods, subjective Drooling Score, personal impression of clinical improvement, and the duration of response were used for the global assessment of sialorrhea after BTX-A treatment. All patients showed objective reduction in saliva production following BTX-A treatment and the mean production was reduced at a significant level. The severity of sialorrhea assessed by Drooling Score was 5.87 +/- 0.92 (range: 5-8) and 3.60 +/- 1.18 (range: 2-6) respectively (pBTX-A injection. The mean duration of BTX-A response extended for 16.3 +/- 5.7 weeks (range: 5-24). No severe adverse effect nor worsening of existing dysphagia was observed in all Parkinsonian patients. Parkinsonian drooling may undermine patient's health and daily activity. BTX-A local injection is a safe and effective measure in counteracting sialorrhea, even in patients associated with moderate dysphagia.

  16. Effects of botulinum toxin A injection and exercise on the growth of juvenile rat gastrocnemius muscle.

    Science.gov (United States)

    Chen, Chen-Ming; Stott, N Susan; Smith, Heather K

    2002-10-01

    Botulinum toxin A (Btx) injections and supervised exercise are often used concurrently to treat calf muscle spasticity in children. This study has analyzed the early effects of Btx-induced paralysis and increased activity by voluntary wheel running on cell growth-related processes in juvenile rat gastrocnemius muscle. Btx injection at 29 days of age prevented the normal increases in wet mass (50%) and fiber cross-sectional area (34%) seen by 36 days of age in control rats. Btx-injected vs. contralateral muscles had 22% fewer myonuclei per fiber length but greater than twofold the number of MyoD-positive nuclei at 36 days of age. The accretion of 5-bromo-2'-deoxyuridine-labeled newly produced myonuclei did not differ between limbs. Voluntary exercise during the 7 days increased the mass (18%) and fiber size (23%) of Btx-injected and contralateral muscles but did not affect any other variable. Thus Btx injection and exercise had early effects on muscle and fiber size without consistently associated changes in myonuclear production or number. This suggests the presence of noncontractile activity-dependent, growth-promoting cytoplasmic events in juvenile muscle.

  17. Botulinum toxin A for palmar hyperhidrosis: assessment with sympathetic skin responses evoked by train of stimuli.

    Science.gov (United States)

    Al-Hashel, J Y; Youssry, D; Rashaed, H M; Shamov, T; Rousseff, R T

    2016-07-01

    Objective assessment of the effect of botulinum toxin A (BT) treatment in primary palmar hyperhidrosis (PH) is attempted by different methods. We decided to use for this purpose sympathetic skin responses evoked by train of stimuli (TSSR). Twenty patients with severe PH (five female, median age 24, range 18-36) were examined regularly over 3 months after receiving 50 UI BT in each palm. TSSR were recorded from the palms after sensory stimulation by a train of three supramaximal electric pulses 3 millisecond apart. Results were compared to longitudinally studied TSSR of 20 healthy sex- and age-matched control subjects. All hyperhidrosis patients reported excellent improvement. TSSR amplitudes decreased at week 1 (mean 54% range 48%-67%) and over the following months in a clinically significant trend (slope R=-.82, P<.0001). TSSR in controls changed insignificantly (±13% from the baseline). The difference between patients and controls was highly significant at any time point (P<.001). This study suggests that TSSR may help in assessment of treatments in PH. It confirms objectively the efficacy of BT in PH.

  18. Use of botulinum toxin type A in symptomatic accessory soleus muscle: first five cases.

    Science.gov (United States)

    Isner-Horobeti, M-E; Muff, G; Lonsdorfer-Wolf, E; Deffinis, C; Masat, J; Favret, F; Dufour, S P; Lecocq, J

    2016-11-01

    Symptomatic accessory soleus muscle (ASM) can cause exercise-induced leg pain due to local nerve/vascular compression, muscle spasm, or local compartment syndrome. As intramuscular injections of botulinum toxin type A (BTX-A) can reduce muscle tone and mass, we investigated whether local BTX-A injections relieve the pain associated with symptomatic ASM. We describe five patients presenting peri/retromalleolar exertional pain and a contractile muscle mass in the painful region. Com-pression neuropathy was ruled out by electromyo-graphic analysis of the lower limb muscles. Doppler ultrasonography was normal, excluding a local vascular compression. ASM was confirmed by magnetic resonance imaging. After a treadmill stress test, abnormal intramuscular pressure values in the ASM, confirmed the diagnosis of compartment syndrome only in one patient. All five patients received BTX-A injections in two points of the ASM. The treatment efficacy was evaluated based on the disappearance of exercise-induced pain and the resumption of normal physical and sports activities. After BTX-A injection, exertional pain disappeared and all five patients resumed their normal level of physical and sports performances. Neither side effects nor motor deficits were observed. BTX-A is well tolerated in patients with ASM and could be used as a new conservative therapeutic strategy for the treatment of symptomatic ASM before surgery.

  19. Knee flexion contracture treated with botulinum toxin type A in patients with haemophilia (PWH).

    Science.gov (United States)

    Daffunchio, C; Caviglia, H; Nassif, J; Morettil, N; Galatro, G

    2016-01-01

    Knee flexion contracture (KFC) remains a common complication of haemoarthrosis in children and young adults with haemophilia. If the KFC is not treated properly it produces disability, postural and gait abnormalities. Evaluate the effectiveness of conservative treatment of KFC with Botulinum toxin type A (BTX-A) in PWH. Seventeen patients were treated, with 21 affected knees. Mean age was 26 years. The mean follow up was 12 months. We evaluated flexion and KFC pretreatment BTX-A and up to 12 months posttreatment. BTX-A application was in hamstring and calf muscles. To evaluate the function, a questionnaire about different activities was made, and it was checked 3, 6 and 12 months after BTX-A. According to the degree of KFC, knees were divided into 3 groups: Group 1: -10° to -30° (n = 10), Group 2: -31° to -45° (n = 6) Group 3: -46° or more (n = 5). The average KFC improved from -38° to -24°. The improvement was 14° (P < 0.001). The average KFC improvement was 9° in group 1, 17° in group 2, and 23° in group 3. There was a high correlation between the improvement in KFC and the total score of the questionnaire R = 0.77. Treatment of KFC with BTX-A improves knee-related functional activities, with the advantage of being a low-cost procedure and easy to apply. © 2015 John Wiley & Sons Ltd.

  20. Botulinum toxin type A chemodenervation treatment in spastic forms of cerebral palsy

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    A. L. Kurenkov

    2013-01-01

    Full Text Available Cerebral palsy (CP is one of the most serious outcomes of the perinatal lesion of central nervous system and the most common reason for neurological disability in children. Being the key cause of pathological dynamic stereotypes that frequently result in pathological posture and contractures, spasticity is critically important for CP. The use of botulinum toxin type A (BTA in complex treatment 2-6 years old CP patients allows significantly to improve motor abilities, help to change the surgical procedure, delay or even avoid some types of surgery. For elder children the use of BTA allows to improve local motor impairment. The treatment of spasticity in CP with BTA is safe (evidence level A and highly effective (evidence level A. It leads to the positive change of pathological dynamic stereotype, significantly improves gait, decreases muscle tone with Ashworth and Tardeu scales and rises the gross motor function score. Our own experience of onabotulinumtoxinA treatment as a part of complex therapy in 68 patients with spastic forms of CP demonstrates the significant improvement of motor function, most noticeable in younger patients(early pre-school age with GMFS I-III.

  1. The use of botulinum toxin in the management of burns itching: preliminary results.

    Science.gov (United States)

    Akhtar, N; Brooks, P

    2012-12-01

    Itching is a common and well recognised problem following burns. As the underlying pathways involved in burns itch have been identified, different pharmacological agents have been introduced to improve the effectiveness of management regimes. We present preliminary data from an on-going study in the use of botulinum toxin as a novel agent in the treatment of this problem. Patients with recalcitrant itching secondary to burns treated with Botox(©) were identified. Data pertaining to burn size, depth and management were recorded. The delay in the onset of the itch, its severity and the speed and duration of any improvement in symptoms were also noted. 10 patients were identified. 1 patient was excluded. Average follow-up was 11.3 months. All patients had deep partial thickness to full thickness burns. Eight patients underwent grafting. The average burn was 24% TBSA. 87.5% of patients rated their burns itch as being severe (>7 on the pain scale). Following the administration of Botox(©) this fell to 0 out of 10 at 4 weeks. The average duration of the symptom free period was nine months (range 3-18 months). Botox(©) can successfully be used to treat burns itch that are resistant to conventional therapies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  2. Predictors of Response to Intradetrusor Botulinum Toxin-A Injections in Patients with Idiopathic Overactive Bladder

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    Brian L. Cohen

    2009-01-01

    Full Text Available Objectives. To evaluate whether there are any demographic or urodynamic differences in patients with idiopathic overactive bladder (I-OAB that respond and do not respond to intradetrusor injections of botulinum toxin-A (BTX-A. Methods. This represents a secondary analysis of data collected from an investigator initiated randomized trial designed to evaluate clinical differences in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Preinjection demographic and urodynamic data were collected. Patients were evaluated 12 weeks after injection and were determined to be responders or nonresponders as defined by our criteria. Statistical comparisons were made between groups. Results. In patients with overactive bladder without incontinence (OAB-Dry, there were no variables that could be used to predict response to BTX-A. On univariate analysis, younger patients with overactive bladder with incontinence (OAB-Wet were more likely to respond to BTX-A than older patients. However, this relationship was no longer statistically significant on multivariate analysis. Conclusions. We were unable to identify any preinjection demographic or urodynamic parameters that could aid in predicting which patients will achieve clinical response to BTX-A. Future studies are necessary to further evaluate this question.

  3. Botulinum toxin therapy for temporomandibular joint disorders: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Chen, Y-W; Chiu, Y-W; Chen, C-Y; Chuang, S-K

    2015-08-01

    The objective of this study was to undertake a systematic review to assess the efficacy of botulinum toxin therapy (BTX) for temporomandibular joint disorders (TMDs). A comprehensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014. Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of randomized controlled trials comparing BTX versus any alternative intervention or placebo. Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations. The entire systematic search and selection process was done independently by two reviewers. Five relevant study trials were identified, involving 117 participants. Two trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal efficacy of pain relief on TMDs, while the remaining two trials showed no significant difference between the BTX and placebo groups. Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed. Based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs. A more rigorous design of trials should be carried out in future studies.

  4. An Open Study of Botulinum-A Toxin Treatment of Idiopathic Trigeminal Neuralgia

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    Karim Nikkhah

    2015-07-01

    Full Text Available Introduction: Trigeminal Neuralgia (TN is a unilateral, recurrent, sharp facial pain disorder that is limited to the distribution of divisions of the trigeminal nerve. The aim of this study was to evaluate the efficacy of Botulinum neurotoxin type A (BTX-A for alleviating the frequency and severity of TN pain. Materials and Methods: This trial was performed as a before and after study. We treated 31 patients (15 male and 16 female with mean age of 52 year old that their diagnosis was made at least 4.5 years before. We injected BTX-A in various parts of face and particularly in the origin of mandibular and maxillary branches of trigeminal nerve. Injection volume was determined by the necessity and pain intensity measured with visual analog scale up to 100U. Patients were evaluated before and after the injection and were followed after week, and each month, for a three months period. Other related variables were recorded such as: toxin complications, pain status variations by brushing, chewing, cold weather and patient’s satisfaction with their therapy. Results: showed that after injection, pain intensity and frequency decreased after tooth brushing, chewing and cold weather (P

  5. Molecular Mechanisms of Treadmill Therapy on Neuromuscular Atrophy Induced via Botulinum Toxin A

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    Sen-Wei Tsai

    2013-01-01

    Full Text Available Botulinum toxin A (BoNT-A is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI, muscle contraction strength, and compound muscle action potential (CMAP amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR subunits α and β was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection.

  6. Tridimensional assessment of adductor spasmodic dysphonia pre- and post-treatment with Botulinum toxin.

    Science.gov (United States)

    Dejonckere, P H; Neumann, K J; Moerman, M B J; Martens, J P; Giordano, A; Manfredi, C

    2012-04-01

    Spasmodic dysphonia voices form, in the same way as substitution voices, a particular category of dysphonia that seems not suited for a standardized basic multidimensional assessment protocol, like the one proposed by the European Laryngological Society. Thirty-three exhaustive analyses were performed on voices of 19 patients diagnosed with adductor spasmodic dysphonia (SD), before and after treatment with Botulinum toxin. The speech material consisted of 40 short sentences phonetically selected for constant voicing. Seven perceptual parameters (traditional and dedicated) were blindly rated by a panel of experienced clinicians. Nine acoustic measures (mainly based on voicing evidence and periodicity) were achieved by a special analysis program suited for strongly irregular signals and validated with synthesized deviant voices. Patients also filled in a VHI-questionnaire. Significant improvement is shown by all three approaches. The traditional GRB perceptual parameters appear to be adequate for these patients. Conversely, the special acoustic analysis program is successful in objectivating the improved regularity of vocal fold vibration: the basic jitter remains the most valuable parameter, when reliably quantified. The VHI is well suited for the voice-related quality of life. Nevertheless, when considering pre-therapy and post-therapy changes, the current study illustrates a complete lack of correlation between the perceptual, acoustic, and self-assessment dimensions. Assessment of SD-voices needs to be tridimensional.

  7. Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin.

    Science.gov (United States)

    Esposito, Marcello; Dubbioso, R; Apisa, P; Allocca, R; Santoro, L; Cesari, U

    2015-09-01

    Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-to-noise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time.

  8. Long-Term Efficacy and Safety of Botulinum Toxin Injections in Dystonia

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    Juan Ramirez-Castaneda

    2013-02-01

    Full Text Available Local chemodenervation with botulinum toxin (BoNT injections to relax abnormally contracting muscles has been shown to be an effective and well-tolerated treatment in a variety of movement disorders and other neurological and non-neurological disorders. Despite almost 30 years of therapeutic use, there are only few studies of patients treated with BoNT injections over long period of time. These published data clearly support the conclusion that BoNT not only provides safe and effective symptomatic relief of dystonia but also long-term benefit and possibly even favorably modifying the natural history of this disease. The adverse events associated with chronic, periodic exposure to BoNT injections are generally minor and self-limiting. With the chronic use of BoNT and an expanding list of therapeutic indications, there is a need to carefully examine the existing data on the long-term efficacy and safety of BoNT. In this review we will highlight some of the aspects of long-term effects of BoNT, including efficacy, safety, and immunogenicity.

  9. No change in calf muscle passive stiffness after botulinum toxin injection in children with cerebral palsy.

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    Alhusaini, Adel A A; Crosbie, Jack; Shepherd, Roberta B; Dean, Catherine M; Scheinberg, Adam

    2011-06-01

    Stiffness and shortening of the calf muscle due to neural or mechanical factors can profoundly affect motor function. The aim of this study was to investigate non-neurally mediated calf-muscle tightness in children with cerebral palsy (CP) before and after botulinum toxin type A (BoNT-A) injection. Sixteen children with spastic CP (seven females, nine males; eight at Gross Motor Function Classification System level I, eight at level II; age range 4-10 y) and calf muscle spasticity were tested before and during the pharmaceutically active phase after injection of BoNT-A. Measures of passive muscle compliance and viscoelastic responses, hysteresis, and the gradient of the torque-angle curve were computed and compared before and after injection. Although there was a slight, but significant increase in ankle range of motion after BoNT-A injection and a small, significant decrease in the torque required to achieve plantigrade and 5° of dorsiflexion, no significant difference in myotendinous stiffness or hysteresis were detected after BoNT-A injection. Despite any effect on neurally mediated responses, the compliance of the calf muscle was not changed and the muscle continued to offer significant resistance to passive motion of the ankle. These findings suggest that additional treatment approaches are required to supplement the effects of BoNT-A injections when managing children with calf muscle spasticity. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

  10. A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor

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    Saifee, Tabish A.; Teodoro, Tiago; Erro, Roberto; Edwards, Mark J.; Cordivari, Carla

    2016-01-01

    Background We aimed to investigate the efficacy and safety of botulinum toxin (BT) injections for jerky action tremor of the upper limb. Methods We performed an uncontrolled, prospective study of electromyography (EMG)-guided BT injections for jerky, position-specific, upper limb action tremor. The primary outcome was clinical global impression at 3–6 weeks after baseline. Results Eight patients with jerky, position-specific action tremor involving the upper limb were consecutively recruited. After a median follow-up of 4.4 weeks (interquartile range [IQR] 3.6–6 weeks), four of them rated themselves as “improved” and two as “much improved.” Five of these six subjects reported improvements in specific activities of daily living (bringing liquids to mouth, feeding, shaving, and dressing). Upper limb subscore of the Fahn–Tolosa–Marin Tremor Rating Scale (FTM) significantly decreased from 4.5 (4–6) to 3 (2–5) (p = 0.01). Discussion This pilot, prospective cohort study suggests that EMG-guided BT injections may improve jerky, position-specific, upper limb action tremor. Placebo-controlled studies evaluating larger samples of patients are warranted to confirm these findings. PMID:27818844

  11. Microfluidic tectonics platform: A colorimetric, disposable botulinum toxin enzyme-linked immunosorbent assay system.

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    Moorthy, Jaisree; Mensing, Glennys A; Kim, Dongshin; Mohanty, Swomitra; Eddington, David T; Tepp, William H; Johnson, Eric A; Beebe, David J

    2004-06-01

    A fabrication platform for realizing integrated microfluidic devices is discussed. The platform allows for creating specific microsystems for multistep assays in an ad hoc manner as the components that perform the assay steps can be created at any location inside the device via in situ fabrication. The platform was utilized to create a prototype microsystem for detecting botulinum neurotoxin directly from whole blood. Process steps such as sample preparation by filtration, mixing and incubation with reagents was carried out on the device. Various microfluidic components such as channel network, valves and porous filter were fabricated from prepolymer mixture consisting of monomer, cross-linker and a photoinitiator. For detection of the toxoid, biotinylated antibodies were immobilized on streptavidin-functionalized agarose gel beads. The gel beads were introduced into the device and were used as readouts. Enzymatic reaction between alkaline phosphatase (on secondary antibody) and substrate produced an insoluble, colored precipitate that coated the beads thus making the readout visible to the naked eye. Clinically relevant amounts of the toxin can be detected from whole blood using the portable enzyme-linked immunosorbent assay (ELISA) system. Multiple layers can be realized for effective space utilization and creating a three-dimensional (3-D) chaotic mixer. In addition, external materials such as membranes can be incorporated into the device as components. Individual components that were necessary to perform these steps were characterized, and their mutual compatibility is also discussed.

  12. Efficacy and Safety of a New Botulinum Toxin Type A Free of Complexing Proteins

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    Hyun-Mi Oh

    2015-12-01

    Full Text Available MT10107 is botulinum neurotoxin type A derived drug which utilizes the 150 kDa portion without complexing proteins and human serum albumin contents. To evaluate the efficacy and the safety of MT10107, it was compared with onabotulinumtoxinA in this double-blind, randomized controlled trial. Twenty-five healthy males received a randomly selected dose of MT10107 into the extensor digitorum brevis (EDB muscle of one foot, and an equivalent dose of onabotulinumtoxinA (BOTOX was injected into the contralateral EDB muscle. While efficacy of the administered substance was determined by measuring paretic effects on the EDB, the local spread of toxin effects was evaluated by the paretic effects on the nearby abductor hallucis (AH and abductor digiti quinti (ADQ muscles. Paretic effects were defined as the percentage of reduction of the compound muscle action potential (CMAP amplitudes, measured at 14, 30, 90 days after the injection, compared to the baseline value. Intergroup (MT10107 and onabotulinumtoxinA differences were not significant in the percentage reduction of the amplitudes in the EDB muscles. In this study, there was no significant difference in efficacy and safety between the two test drugs. MT10107 may be effective and safe as much as onabotulinumtoxinA to produce the desired paretic effect.

  13. Botulinum toxin type A and cervical dystonia: a seven-year follow-up

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    Carlos Henrique F. Camargo

    2011-10-01

    Full Text Available Most cases of cervical dystonia (CD are idiopathic, and focal injections of botulinum toxin A (BoNT/A are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS at baseline assessment (2001-2002 and follow-up (2008-2009 was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6±6.6 and 17.7±4.8; p<0.05. There was no improvement in the severity of cervical pain (p=0.43. In conclusion, BoNT/A was a safe and effective long-term therapy for CD.

  14. Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain

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    Young Eun Moon

    2016-01-01

    Full Text Available Neuropathic pain includes postherpetic neuralgia (PHN, painful diabetic neuropathy (PDN, and trigeminal neuralgia, and so on. Although various drugs have been tried to treat neuropathic pain, the effectiveness of the drugs sometimes may be limited for chronic intractable neuropathic pain, especially when they cannot be used at an adequate dose, due to undesirable severe side effects and the underlying disease itself. Botulinum toxin type A (BoNT-A has been known for its analgesic effect in various pain conditions. Nevertheless, there are no data of nerve block in PHN and PDN. Here, we report two patients successfully treated with ultrasound-guided peripheral nerve block using BoNT-A for intractable PHN and PDN. One patient had PHN on the left upper extremity and the other patient had PDN on a lower extremity. Due to side effects of drugs, escalation of the drug dose could not be made. We injected 50 Botox units (BOTOX®, Allergan Inc., Irvine, CA, USA into brachial plexus and lumbar plexus, respectively, under ultrasound. Their pain was significantly decreased for about 4–5 months. Ultrasound-guided nerve block with BoNT-A may be an effective analgesic modality in a chronic intractable neuropathic pain especially when conventional treatment failed to achieve adequate pain relief.

  15. CLINICAL APPLICATION OF BOTULINUM TOXIN TYPE B IN MOVEMENT DISORDERS AND AUTONOMIC SYMPTOMS

    Institute of Scientific and Technical Information of China (English)

    Xin-hua Wan; Kevin Dat Vuong; Joseph Jankovic

    2005-01-01

    Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sialorrhea and hyperhidrosis.Methods A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 ± 0.8 years. Results of the first and last treatment of patients with at least 3injection sessions were compared.Results The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response.The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection sessions (mean 10 ± 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment.Conclusios Though most patients require increased dosage to maintain effective response after repeated injections,BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.

  16. [Botulinum toxin type A contribution in the treatment of Raynaud's phenomenon due to systemic sclerosis].

    Science.gov (United States)

    Serri, J; Legré, R; Veit, V; Guardia, C; Gay, A-M

    2013-12-01

    Raynaud's phenomenon is a vasospastic disorder of the extremities that can lead, in the hands, to pain, disability, ischemic ulcers and digital chronic ischemia. Medical and surgical current treatments are not fully effective while causing side effects. Recent studies have emphasized the value of botulinum toxin type A (BTX A) in the management of primary Raynaud's phenomenon. The originality of Raynaud's syndrome secondary to systemic sclerosis is to combine both arterial vasospasm and sclerosis of the arterial wall, what is supposed to reduce BTX A effects. The purpose of this work is to evaluate BTX A efficiency in patients with Raynaud's phenomenon secondary to systemic sclerosis. We performed a prospective study for 12 months. Patients with severe Raynaud's phenomenon due to systemic sclerosis were injected with BTX A in the two hands. Evolution of ischemic ulcers, QuickDASH Score, O2 partial pressure, pain were measured before and 30 days after injection. We treated 18 patients. Thirty days after injection, we noticed a complete healing of ulcers, QuickDASH Score was improved from 39.4 to 20, as the O2 partial pressure from 16 to 42 mmHg and the pain from VNS from 6/10 to 2/10. BTX A appears to improve significantly Raynaud's phenomenon symptomatology in patients with systemic sclerosis despite the component of arterial sclerosis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity.

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    Gutiérrez-Martín, P; Vírseda-Chamorro, M; Salinas Casado, J; Gómez-Rodríguez, A; Esteban-Fuertes, M

    2015-05-01

    To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. The BTX-A significantly increased (p lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Unique use of botulinum toxin to decrease adductor tone and allow surgical excision of vulvar carcinoma.

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    Guo, Y; Shin, K

    2004-01-01

    Here, we present the case of an 86-year-old woman with vulvar carcinoma requiring surgical resection and with Parkinson's disease with severe spasticity and contractures of the lower extremities. Because of the patient's severe contractures and spasticity (her knees could only be separated by 2 cm with sustained abducting force), surgical positioning and access to the vulva were impossible. The patient was admitted, intending to undergo surgery after injection with botulinum toxin (BTX) to hip adductors and intensive physical therapy. After confirmed healed hip arthroplasty, the patient underwent BTX injection (400 U) to her bilateral adductor brevis, adductor longus, adductor magnus, and semimembranosus and semitendinosus muscles on day 2 of her hospital stay. On day 3, a physical therapist began a twice-a-day stretching program. An adjustable abduction brace was custom-made to provide sustained stretching. On day 9, the patient underwent wide local excision of vulvar carcinoma with the abductor brace in place. The patient tolerated the surgery well and was discharged home on day 11 with continuous physical therapy. Upon discharge, the distance between the patient's knees was 14 cm. This unique case demonstrated a new indication for BTX treatment in the preoperative setting to allow surgical positioning and access.

  19. Use of botulinum toxin-A for musculoskeletal pain in patients with whiplash associated disorders [ISRCTN68653575

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    Juan Francisco J

    2004-02-01

    Full Text Available Abstract Background Whiplash associated disorder is commonly linked to motor vehicle accidents and sports injuries. Cervical injury is attributed to rapid extension followed by neck flexion. The exact pathophysiology of whiplash is uncertain but probably involves some degree of aberrant muscle spasms and may produce a wide range of symptoms. The most commonly prescribed pharmacological agents for initial treatment of whiplash-associated pain are oral muscle relaxants and nonsteroidal anti-inflammatory drugs. However, potential systemic adverse effects limit these agents. Physical interventions such as mobilization, manipulation, and exercises have proved beneficial for pain and dysfunction but only on a time-limited basis. Little evidence suggests that physical therapy specifically aimed at the musculature (e.g., transcutaneous electrical nerve stimulation, ultrasonography, heat, ice, and acupuncture improves prognosis in acute whiplash associated disorder. A new approach to treatment is the use of botulinum toxin, which acts to reduce muscle spasms. Methods/design This is a prospective, randomized, controlled clinical trial and botulinum toxin-A (Botox® injections will be compared with placebo injections. The primary objective is to determine the efficacy of Botox® in the management of musculoskeletal pain in whiplash associated disorders. Discussion Botulinum toxin type-A toxin has been studied in small trials on whiplash associated disorder patients and has generally been found to relieve pain and improve range of motion. Specifically, we seek to assess the efficacy of Botox® in reducing pain and to improve the cervical spine range of movement, during the 6-month trial period.

  20. Structural And Biochemical Studies of Botulinum Neurotoxin Serotype C1 Light Chain Protease: Implications for Dual Substrate Specificity

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    Jin, R.; Sikorra, S.; Stegmann, C.M.; Pich, A.; Binz, T.; Brunger, A.T.

    2009-06-01

    Clostridial neurotoxins are the causative agents of the neuroparalytic disease botulism and tetanus. They block neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs) SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery. The catalytic component of the clostridial neurotoxins is their light chain (LC), a Zn2+ endopeptidase. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), termed serotype A to G, and tetanus neurotoxin (TeNT). Each of them exhibits unique specificity for their target SNAREs and peptide bond(s) they cleave. The mechanisms of action for substrate recognition and target cleavage are largely unknown. Here, we report structural and biochemical studies of BoNT/C1-LC, which is unique among BoNTs in that it exhibits dual specificity toward both syntaxin and SNAP-25. A distinct pocket (S1') near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin. Mutations of this SNAP-25 residue dramatically reduce enzymatic activity. The remote a-exosite that was previously identified in the complex of BoNT/A-LC and SNAP-25 is structurally conserved in BoNT/C1. However, mutagenesis experiments show that the a-exosite of BoNT/C1 plays a less stringent role in substrate discrimination in comparison to that of BoNT/A, which could account for its dual substrate specificity.

  1. Neurotoxins from Clostridium botulinum (serotype A) isolated from the soil of Mendoza (Argentina) differ from the A-Hall archetype and from that causing infant botulism.

    Science.gov (United States)

    Caballero, P; Troncoso, M; Patterson, S I; López Gómez, C; Fernandez, R; Sosa, M A

    2016-10-01

    The type A of neurotoxin produced by Clostridium botulinum is the prevalent serotype in strains of Mendoza. The soil is the main reservoir for C.botulinum and is possibly one of the infection sources in infant botulism. In this study, we characterized and compared autochthonous C. botulinum strains and their neurotoxins. Bacterial samples were obtained from the soil and from fecal samples collected from children with infant botulism. We first observed differences in the appearance of the colonies between strains from each source and with the A Hall control strain. In addition, purified neurotoxins of both strains were found to be enriched in a band of 300 kDa, whereas the A-Hall strain was mainly made up of a band of ∼600 kDa. This finding is in line with the lack of hemagglutinating activity of the neurotoxins under study. Moreover, the proteolytic activity of C. botulinum neurotoxins was evaluated against SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins from rat brain. It was observed that both, SNAP 25 (synaptosomal-associated protein 25) and VAMP 2 (vesicle-associated membrane protein) were cleaved by the neurotoxins isolated from the soil strains, whereas the neurotoxins from infant botulism strains only induced a partial cleavage of VAMP 2. On the other hand, the neurotoxin from the A-Hall strain was able to cleave both proteins, though at a lesser extent. Our data indicate that the C.botulinum strain isolated from the soil, and its BoNT, exhibit different properties compared to the strain obtained from infant botulism patients, and from the A-Hall archetype. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

    Science.gov (United States)

    Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

    2017-03-01

    The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B7) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B7 components of C2 toxin and LT, C2IIa and PA63, respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

  3. Striving for more good days: patient perspectives on botulinum toxin for the treatment of cervical dystonia

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    Poliziani M

    2016-08-01

    flexible treatment. Conclusion: The high burden of recurring primary and secondary symptoms of CD considerably affects patients’ quality of life. Patient-led assessments of disease burden revealed that personalized, more flexible, and/or shorter BoNT injection intervals may reduce the day-to-day impact of CD. Collaboration between patients, clinicians, and health care systems may effect change and improve treatment for patients with CD. Keywords: botulinum toxin type A, cervical dystonia, patient survey, spasmodic torticollis, treatment satisfaction

  4. Approaches to treatment of emerging Shiga toxin-producing Escherichia coli infections highlighting the O104:H4 serotype.

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    Rahal, Elias A; Fadlallah, Sukayna M; Nassar, Farah J; Kazzi, Natalie; Matar, Ghassan M

    2015-01-01

    Shiga toxin-producing Escherichia coli (STEC) are a group of diarrheagenic bacteria associated with foodborne outbreaks. Infection with these agents may result in grave sequelae that include fatality. A large number of STEC serotypes has been identified to date. E. coli serotype O104:H4 is an emerging pathogen responsible for a 2011 outbreak in Europe that resulted in over 4000 infections and 50 deaths. STEC pathogenicity is highly reliant on the production of one or more Shiga toxins that can inhibit protein synthesis in host cells resulting in a cytotoxicity that may affect various organ systems. Antimicrobials are usually avoided in the treatment of STEC infections since they are believed to induce bacterial cell lysis and the release of stored toxins. Some antimicrobials have also been reported to enhance toxin synthesis and production from these organisms. Various groups have attempted alternative treatment approaches including the administration of toxin-directed antibodies, toxin-adsorbing polymers, probiotic agents and natural remedies. The utility of antibiotics in treating STEC infections has also been reconsidered in recent years with certain modalities showing promise.

  5. Outcomes of intra-detrusor injections of botulinum toxin in patients with spina bifida: A systematic review.

    Science.gov (United States)

    Hascoet, Juliette; Manunta, Andrea; Brochard, Charlène; Arnaud, Alexis; Damphousse, Mireille; Menard, Hélène; Kerdraon, Jacques; Journel, Hubert; Bonan, Isabelle; Odent, Sylvie; Fremond, Benjamin; Siproudhis, Laurent; Gamé, Xavier; Peyronnet, Benoit

    2017-03-01

    Bladder management in spina bifida patients relies on clean intermittent catheterization and oral antimuscarinics with a significant failure rate. The efficacy of intradetrusor injections of botulinum toxin has been confirmed in patients with spinal cord injury or multiple sclerosis but not in patients with myelomeningocele. To conduct a systematic review of current evidence regarding the efficacy of intra-detrusor injections of Botulinum Toxin A (BTX-A) in spina bifida patients with neurogenic detrusor overactivity (NDO) refractory to antimuscarinics. A research has been conducted on Medline and Embase using the keywords: ("spina bifida" OR "myelomeningocele" OR "dysraphism") AND "toxin." The search strategy and studies selection were performed using the PICOS method according to the PRISMA statement. Twelve published series were included (n = 293 patients). All patients were spina bifida but this assumption is not supported by high level of evidence studies. There is no data available in adult patients. Neurourol. Urodynam. 36:557-564, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Botulinum toxin A injection for chronic anal fissures and anal sphincter spasm improves quality of life in recessive dystrophic epidermolysis bullosa

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    Cassandra Chaptini, MBBS

    2015-12-01

    Full Text Available We report a 20-year-old female with generalized, severe, recessive dystrophic epidermolysis bullosa who developed secondary chronic anal fissures. This resulted in anal sphincter spasm and severe, disabling pain. She was treated with five botulinum toxin A injections into the internal anal sphincter over a period of 2 years and gained marked improvement in her symptoms. This case demonstrates the successful use of botulinum toxin A injections to relieve anal sphincter spasm and fissuring, with long-term improvement.

  7. Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series

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    Delanois Ronald E

    2009-08-01

    Full Text Available Abstract Background Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty. Methods Ten patients (14 hips who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks. Results At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees. Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points prior to injection to a mean of 96 points (range, 93 to 98 at final follow-up. There were no serious treatment-related adverse events. Conclusion Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy.

  8. Impact of botulinum toxin a on the quality of life of subjects following treatment of facial lines.

    Science.gov (United States)

    Jandhyala, Ravi

    2013-09-01

    To investigate quality of life and its correlation to patient satisfaction before and after treatment with botulinum toxin A. Quality of life was assessed using the Schedule for the Evaluation of Individual Quality of Life Direct-Weighting tool. Patients identified the five areas of their life of the greatest importance to them, weighted the areas as to their relative importance, and rated their status in each area on a visual scale before treatment (old cues) and 28 days later (using both old cues and newly defined and weighted cues). At both visits, patients also rated their overall quality of life using a visual analogue scale. Patient satisfaction with their appearance was measured using a 10-point scale in conjunction with standardized photographs taken at each visit. Fifty-three patients (median age 39.5 years; 87% women) with moderate-to-severe wrinkles of the glabella, forehead, or crow's feet were enrolled. Treatment with incobotulinumtoxinA consistently resulted in a significant improvement in quality of life according to Schedule for the Evaluation of Individual Quality of Life Direct-Weighting tool index scores (old cues, P=0.0006; new cues P=0.0235) and patient assessment of their overall quality of life (Pfinance, relationships, and health were the five most frequently identified cues at each assessment. No correlation between quality of life and satisfaction scores was found, although both were significantly increased after treatment. These results support the contention that quality of life is significantly improved following botulinum toxin A treatment and that consideration should be given to incorporating the measurement of quality of life as an outcome measure following botulinum toxin A treatment, especially as satisfaction does not correlate to quality of life.

  9. More than a black box of rehabilitation: Characterizing therapy programmes following botulinum toxin injections for spasticity in adults with stroke.

    Science.gov (United States)

    Demetrios, Marina; Brand, Caroline; Louie, Julie; Khan, Fary

    2016-04-28

    To describe ambulatory rehabilitation programmes (physical and occupational therapy activities and interventions) following botulinum toxin injections for post-stroke spasticity using a stroke rehabilitation taxonomy. To explore the relationship between therapy provided and injected limb/s and treatment goals. Prospective, observational cohort study. Stroke survivors (n = 47) participating in ambulatory rehabilitation programmes following botulinum toxin injections for upper limb, lower limb or upper and lower limb spasticity. Standardized therapy documentation forms were completed prospectively for each occupational and physical therapy session. Main outcomes were the proportion of total therapy time spent in various therapeutic activities; total sessions during which each intervention was used to facilitate the activities most time was spent in; and goals related to each activity category. Sub-analysis was carried out for participants, based on limb/s injected. Most time was spent in "upper extremity control" activities as the upper limb was more often injected. A large proportion of therapy time was spent in activities remediating "performance skills or body structure and function impairments". In the upper and lower limb, and upper limb groups 38.7% and 46.2% of goals, respectively, related to this activity category, but less than 10% in the lower limb group. Little time was spent in community participation and leisure activities, whilst over one-third of lower limb group goals related to this category. Ambulatory rehabilitation programmes following botulinum toxin injections for post-stroke spasticity varied depending on limb/s injected and reflected treatment goals to some extent.

  10. [Botulinum toxin to treat sweat caused sequelae in patients with hearing aids, active middle ear implants and cochlear implants].

    Science.gov (United States)

    Laskawi, R; Winterhoff, J; Blum, J; Matthias, C

    2012-11-01

    The production of sweat in the temporal skin region may be a serious problem for patients with hearing aids, active middle ear implants or cochlear implants. We report on two patients suffering from a loss of function of their hearing aid and a reduction of the "wear comfort" of an active middle ear implant. The patients underwent intracutaneous botulinum toxin (BTX) treatment of the temporal skin region. In both patients a distinct improvement of their complaints occurred, enabling them to use their hearing aids and active middle ear implants continuously. BTX injections are suited to improve sweat-caused complaints in patients with hearing aids, active middle ear implants and cochlear implants.

  11. The Effect and Complication of Botulinum Toxin Type A Injection with Serial Casting for the Treatment of Spastic Equinus Foot

    OpenAIRE

    Lee, Sook Joung; Sung, In Young; Jang, Dae Hyun; Yi, Jin Hwa; Lee, Jin Ho; Ryu, Ju Seok

    2011-01-01

    Objective To identify the effect of serial casting combined with Botulinum toxin type A (BTX-A) injection on spastic equinus foot. Method Twenty-nine children with cerebral palsy who had equinus foot were recruited from the outpatient clinic of Rehabilitation Medicine. The children were divided into 2 groups, one of which received serial casting after BTX-A injection, and the other which only received BTX-A injection. Serial casting started 3 weeks after the BTX-A injection, and was changed w...

  12. Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction.

    Science.gov (United States)

    Janicki, Joseph J; Chancellor, Michael B; Kaufman, Jonathan; Gruber, Michele A; Chancellor, David D

    2016-03-18

    Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

  13. An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

    Science.gov (United States)

    Alfonsi, E; Merlo, I M; Ponzio, M; Montomoli, C; Tassorelli, C; Biancardi, C; Lozza, A; Martignoni, E

    2010-01-01

    Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

  14. Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-deficient rabbit.

    Science.gov (United States)

    Longino, David; Frank, Cy; Herzog, Walter

    2005-11-01

    We established botulinum type-A toxin (BTX-A) injections as a powerful tool to cause knee extensor weakness in New Zealand White (NZW) rabbits. The purpose of this study was to determine if BTX-A induced quadriceps weakness causes muscle dysfunction beyond that caused by anterior cruciate ligament (ACL) transection in the knee of NZW rabbits. Twenty animals were randomly divided into four study groups (n=5 each); uninjected controls, BTX-A injection alone, ACL transection alone, BTX-A injection and ACL transection combined. Isometric knee extensor torque, quadriceps muscle mass, and vertical and anterior-posterior ground reaction forces were measured four weeks post single (BTX-A and ACL), unilateral intervention. Muscle weakness, muscle atrophy and decrease in ground reaction forces were all significantly greater for the experimental compared to the untreated contralateral legs. BTX-A injection produced a greater deficit in quadriceps mass and knee extensor torque than ACL transection alone, but produced smaller deficits in the ground reaction forces. ACL transection superimposed on BTX-A injection did not change either knee extensor torque production or muscle mass. Together these results suggest that BTX-A injection causes great force and muscle mass deficits, and affects functional gait in a significant manner, but it has no measurable functional effect when superimposed on ACL transection, at least not in the acute protocol tested here. Hopefully, BTX-A injection for acutely enhancing the degree of muscle weakness in otherwise untreated animals, or in experimental models of osteoarthritis, will help in investigating the role of muscle weakness in joint degeneration.

  15. Botulinum toxin type-B improves sialorrhea and quality of life in bulbaronset amyotrophic lateral sclerosis.

    Science.gov (United States)

    Costa, João; Rocha, Maria Luz; Ferreira, Joaquim; Evangelista, Teresinha; Coelho, Miguel; de Carvalho, Mamede

    2008-04-01

    Sialorrhea is a disabling problem in bulbaronset amyotrophic lateral sclerosis (ALS). Botulinum toxin (BTX) type A and B have been proposed as alternatives to traditional treatments. To evaluate the efficacy and safety of BTX type B in the treatment of sialorrhea in patients with bulbar-onset ALS. Open-label prospective study of BTX type B injections in parotids (1000 U) and submandibular (250 U) glands using anatomic landmarks. Primary outcome was rate of responders (improvement > 50% on visual analogue scales (VAS) of severity and disability of sialorrhea) 1 month post-treatment. Other outcomes included subjective (drooling and quality of daily living questionnaires) and objective (cotton roll weights and number of paper handkerchiefs used) evaluations. Safety evaluations included questionnaires regarding brain stem symptoms. Sixteen ALS patients were included. At 1 month the rate of responders was 75% with a mean reduction of 70% in severity and disabling VASs. Fifteen patients (94 %) reported some benefit with drooling reduction. In objective measurements there was a reduction over 60 % in saliva production and in the number of handkerchiefs used. Onset of effect occurred within 3 days. Most patients reported better quality of living. The most frequent side-effects were viscous saliva, local pain, chewing weakness and respiratory infection. There were no changes in blood pressure or cardiac rate. At 3 months, there was still a positive effect in all outcomes. All patients except one manifested their willingness to repeat treatment. Anatomic guided BTX type B injections seem effective and safe to treat sialorrhea in bulbar-onset ALS.

  16. Long-lasting benefits of botulinum toxin type B in Parkinson's disease-related drooling.

    Science.gov (United States)

    Lagalla, Giovanni; Millevolte, Marzia; Capecci, Marianna; Provinciali, Leandro; Ceravolo, Maria Gabriella

    2009-04-01

    To investigate the safety, efficacy and effectiveness of botulinum toxin type-B (BTX-B) injections into the parotid glands to reduce drooling in Parkinson's disease (PD) subjects. A double-blind, randomised, placebo-controlled study enrolled 36 advanced phase PD subjects who complained of disabling drooling. Patients received either 4000U BTX-B or placebo. Anatomically guided injections were performed. Outcome measures were chosen to assess both the subjective feeling of improvement (i. e. the Drooling Severity and Frequency Scale, DSFS, visuo-analogic ratings of familial distress, VAS-FD, and social distress, VAS-SD) and objective saliva reduction (saliva production over five minutes was checked by weighing dental rolls). The Global Impression Score (GIS) was also applied, rating improvement from 0 to 3. One month after injections, BTX-B patients showed a meaningful improvement in almost all subjective outcomes. Two-way analysis of variance gave a significant time x treatment effect, F-value being 52.5 (p BTX-B subjects declared sialorrhea reduction of any kind (moderate for 44.4% cases, and dramatic for 33.3% subjects), at variance with 61.1% controls who denied any benefit from treatment. (Chi-square = 22.9; p BTX-B group compared to 6.7 +/- 1.4 weeks in controls (T-value: 26.4; p < 0.0001). BTXB represents a safe and efficacious tool for the management of PD-related drooling, ensuring a longlasting waning of this disabling symptom.

  17. Intraglandular injection of botulinum toxin a reduces tear production in rabbits.

    Science.gov (United States)

    Demetriades, Anna M; Leyngold, Ilya M; D'Anna, Sam; Eghrari, Allen O; Emmert, Dave G; Grant, Michael P; Merbs, Shannath L

    2013-01-01

    To develop an animal model and investigate the dose-dependent effect of an intraglandular injection of botulinum toxin A (BTX-A) on tear production. In a volume of 0.1-ml, 0.625-, 1.25-, or 2.5-U BTX-A was injected transconjunctivally in the superolateral lobe of the lacrimal gland of adult New Zealand white female rabbits. In the contralateral lacrimal gland, 0.1 ml of 0.9% sodium chloride was injected. Prior to injection and at 1-week postinjection, photographs were taken to evaluate pre- and postoperative eyelid position. Fluorescein and Rose Bengal stain were used to evaluate the corneal surface, and Schirmer test was used to assess tear production. Glands injected with the intermediate (1.25 U) and the highest (2.5 U) doses of BTX-A displayed a statistically significant decrease in tear production (p = 0.002 and 0.007, respectively) compared with the contralateral saline-injected glands at 1 week. No corneal pathologic factors from excessive dryness were observed following the injection. While postinjection ptosis was observed (p = 0.025), no difference was seen between BTX-A and saline-injected eyes. In rabbits, intraglandular injection of BTX-A resulted in decreased tear production at 1 week. No additional reduction in tear production was seen with a BTX-A dose greater than 1.25 U, suggesting glandular receptor saturation at this dose. Despite suppression of tear production, no corneal pathologic factors were observed. Further studies are needed to refine this animal model with the ultimate goal of determining optimum delivery route and concentration to reduction in tear production while minimizing side effects in patients.

  18. Budget impact analysis of botulinum toxin A therapy for upper limb spasticity in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Abogunrin S

    2015-04-01

    Full Text Available Seye Abogunrin,1 Linda Hortobagyi,2 Edit Remak,3 Jerome Dinet,4 Sylvie Gabriel,5 Abdel Magid O Bakheit6 1Meta Research, 2Health Economics, Evidera, London, UK; 3Health Economics, Evidera, Budapest, Hungary; 4Health Economics and Outcomes Research (Global, 5Global Market Access and Pricing, Ipsen Pharma, Boulogne-Billancourt, France; 6Neurological Rehabilitation, Moseley Hall Hospital, Birmingham, UK Background: Botulinum toxin A (BoNT-A is an effective treatment for patients with upper limb spasticity (ULS, which is a debilitating feature of upper motor neuron lesions. BoNT-A preparations available in the UK are associated with different costs. Methods: We developed a budget impact model to assess the effect of changing market shares of different BoNT-A formulations – abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA – and best supportive care, from the UK payer perspective, over a 5-year time horizon. Epidemiological and resource use data were derived from published literature and clinical expert opinion. One-way sensitivity analyses were performed to determine parameters most influential on budget impact. Results: Base-case assumptions showed that an increased uptake of abobotulinumtoxinA resulted in a 5-year savings of £6,283,829. Treatment with BoNT-A costs less than best supportive care per patient per year, although treating a patient with onabotulinumtoxinA (£20,861 and incobotulinumtoxinA (£20,717 cost more per patient annually than with abobotulinumtoxinA (£19,800. Sensitivity analyses showed that the most influential parameters on budget were percentage of cerebral palsy and stroke patients developing ULS, and the prevalence of stroke. Conclusion: Study findings suggest that increased use of abobotulinumtoxinA for ULS in the UK could potentially reduce total ULS cost for the health system and society. Keywords: stroke, cerebral palsy, multiple sclerosis, traumatic brain injury 

  19. Botulinum toxin in migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents.

    Science.gov (United States)

    Ramachandran, Roshni; Lam, Carmen; Yaksh, Tony L

    2015-07-01

    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi)-SO capsaicin (20 μl of 0.5mM solution) or meningeal capsaicin (4 μl of 0.35 μM). Pre-treatment with ipsi-SO BoNT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; and vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent.

  20. Best Clinical Practice in Botulinum Toxin Treatment for Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Walter Strobl

    2015-05-01

    Full Text Available Botulinum toxin A (BoNT-A is considered a safe and effective therapy for children with cerebral palsy (CP, especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.

  1. Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    S. Deffontaines-Rufin

    2011-10-01

    Full Text Available PURPOSE: Neurogenic detrusor overactivity (NDO is common in patients who suffer from multiple sclerosis (MS. When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. MATERIALS AND METHODS: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor, improvement, or total failure (urge incontinence and overactive detrusor. RESULTS: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001, maximum cystometric capacity (p = 0.0035, maximum detrusor pressure (p = 0.0000001. 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015. CONCLUSIONS: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.

  2. Injection of botulinum toxin for the treatment of post-laryngectomy pharyngoesophageal spasm-related disorders

    Science.gov (United States)

    Lightbody, KA; Wilkie, MD; Kinshuck, AJ; Gilmartin, E; Lewis-Jones, H; Jones, TM; Lancaster, J

    2015-01-01

    Introduction Pharyngoesophageal spasm (PES) can cause dysphagia, central valve leak (CVL), and dypshonia in post-laryngectomy patients. Botulinum toxin has been used effectively for the treatment of PES, but data regarding patient-reported outcomes and efficacy for CVL are limited. We evaluated the results of botox injection for PES spasm using subjective and objective measures. Methods Data were collected prospectively (February 2010 to August 2013) on 13 patients undergoing botox injection for PES as identified by video fluoroscopy. We collected digital voice recordings, air-pressure measurements (APMs) for speech, and quality of life (QoL) data before and after the procedure: University of Washington QoL questionnaire (UW-QoL), MD Anderson Swallowing Inventory (MDADI) and the Voice Handicap Index (VHI-30). Results APMs for a sustained vowel decreased by 18% after botox injection, whereas maximum phonatory times increased by 63% (mean increase, 8 to 13 seconds). Sustained vowel amplitude decreased (mean, 87db to 83db) with an associated reduction in sustained vowel frequency (117Hz to 77Hz). MDADI scores improved by 10.2% overall, and UW-QoL scores showed an improvement in score of 7.6%. Mean scores for VHI-30 deteriorated by 2% overall but, when considering only those patients experiencing dysphonia, an improvement of 9.4% was seen. There was an overall net reduction for the CVL cohort of 12 speech valves in the year after injection. Conclusions Our series confirm the safety and objective efficacy of botox injection for PES. QoL measurements were less convincing, and this disparity between subjective and objective measurements must be considered when treating such patients. PMID:26414361

  3. Cellular and Matrix Response of the Mandibular Condylar Cartilage to Botulinum Toxin

    Science.gov (United States)

    Dutra, Eliane H.; O’ Brien, Mara H.; Lima, Alexandro; Kalajzic, Zana; Tadinada, Aditya; Nanda, Ravindra; Yadav, Sumit

    2016-01-01

    Objectives To evaluate the cellular and matrix effects of botulinum toxin type A (Botox) on mandibular condylar cartilage (MCC) and subchondral bone. Materials and Methods Botox (0.3 unit) was injected into the right masseter of 5-week-old transgenic mice (Col10a1-RFPcherry) at day 1. Left side masseter was used as intra-animal control. The following bone labels were intraperitoneally injected: calcein at day 7, alizarin red at day 14 and calcein at day 21. In addition, EdU was injected 48 and 24 hours before sacrifice. Mice were sacrificed 30 days after Botox injection. Experimental and control side mandibles were dissected and examined by x-ray imaging and micro-CT. Subsequently, MCC along with the subchondral bone was sectioned and stained with tartrate resistant acid phosphatase (TRAP), EdU, TUNEL, alkaline phosphatase, toluidine blue and safranin O. In addition, we performed immunohistochemistry for pSMAD and VEGF. Results Bone volume fraction, tissue density and trabecular thickness were significantly decreased on the right side of the subchondral bone and mineralized cartilage (Botox was injected) when compared to the left side. There was no significant difference in the mandibular length and condylar head length; however, the condylar width was significantly decreased after Botox injection. Our histology showed decreased numbers of Col10a1 expressing cells, decreased cell proliferation and increased cell apoptosis in the subchondral bone and mandibular condylar cartilage, decreased TRAP activity and mineralization of Botox injected side cartilage and subchondral bone. Furthermore, we observed reduced proteoglycan and glycosaminoglycan distribution and decreased expression of pSMAD 1/5/8 and VEGF in the MCC of the Botox injected side in comparison to control side. Conclusion Injection of Botox in masseter muscle leads to decreased mineralization and matrix deposition, reduced chondrocyte proliferation and differentiation and increased cell apoptosis in the

  4. The efficiency of high dose botulinum toxin type-A in the treatment of cerebral palsy

    Directory of Open Access Journals (Sweden)

    Alper İbrahim Dai

    2014-03-01

    Full Text Available Objective: Cerebral palsy is the most common cause of severe physical disability in childhood. Botulinum toxin type A (BTX-A, has rapidly gained acceptance as a different treatment for spasticity. However, no consensus exists among clinicians about optimal dose of BTX-A in pediatric patients. Doses of 2-6 U/ kg bodyweight with a maximum total dose of 29U/kg have been reported. This study was conducted due to uncertain dosage rage in pediatric use. Method: In this study, 12 patients with cerebral palsy and spastic eqinus foot deformity who referred to our center, were treated with BTX-A in the dosage of 25 U/kg. After treatment of BTX-A, patients were followed up total of 6 months. Three months after treatment, Gross motor functional measurement (GMFM and Modified Ashwort scale (MAS were done. At the same time, questionnaires (PCQ were filled for possible side effects. Results: Average age of 6 girls and 6 boys were 4.5 ± 2.8 years. GMFM and MAS were done before and 3 months after treatment and were found statistically significant (p<0.05. Muscle soreness was the most common symptom at PCQ forms. Conclusion: Using these two objective scales and PCQ form, high dose of BTX-A treatment was found statistically successful. Larger dose of BTX-A was used which was considered safe, effective and better tolerated by children. Titration of the dose of BTX-A, should be individualized for each patient due to different level of spasticity affecting patients in different ways. J Clin Exp Invest 2014; 5 (1: 93-97

  5. Preoperative progressive pneumoperitoneum and botulinum toxin type A in patients with large incisional hernia.

    Science.gov (United States)

    Bueno-Lledó, J; Torregrosa, A; Ballester, N; Carreño, O; Carbonell, F; Pastor, P G; Pamies, J; Cortés, V; Bonafé, S; Iserte, J

    2017-04-01

    Combination of preoperative progressive pneumoperitoneum (PPP) and botulinum toxin type A (BT) has not been previously reported in the management of large incisional hernia (LIH). Observational study of 45 consecutive patients with LIH between June 2010 and July 2014. The diameters of the hernia sac, the volumes of the incisional hernia (VIH) and the abdominal cavity (VAC), and the VIH/VAC ratio were measured before and after PPP and BT using abdominal CT scan data. We indicated the combination of both techniques when the volume of the incisional hernia (VIH)/volume of the abdominal cavity (VAC) ratio was >20%. The median insufflated volume of air for PPP was 8.600 ± 3.200 cc (4.500-13.250), over a period of 14.3 ± 1.3 days (13-16). BT administration time was 40.2 ± 3.3 days (37-44). We obtained an average value of reduction of 14% of the VIH/VAC ratio after PPP and BT (p < 0.05). Complications associated with PPP were 15.5%, and with surgical technique, 26.6%. No complications occurred during the BT administration. Reconstructive technique was anterior CST and primary fascial closure was achieved in all patients. Median follow-up was 40.5 ± 19 months (12-60) and we reported 2 cases of hernia recurrence (4.4%). Preoperative combination of PPP and BT is feasible and a useful tool in the surgical management of LIH, although at the cost of some specific complications.

  6. Botulinum toxin induces muscle paralysis and inhibits bone regeneration in zebrafish.

    Science.gov (United States)

    Recidoro, Anthony M; Roof, Amanda C; Schmitt, Michael; Worton, Leah E; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J; Srinivasan, Sundar; Moon, Randall T; Gardiner, Edith M; Kaminsky, Werner; Bain, Steven D; Allan, Christopher H; Gross, Ted S; Kwon, Ronald Y

    2014-11-01

    Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (eg, development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study, we developed a model of BTx-induced muscle paralysis in adult zebrafish, and we examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders.

  7. Intramuscular nerve distribution patterns of anterior forearm muscles in children: a guide for botulinum toxin injection.

    Science.gov (United States)

    Yang, Fangjiu; Zhang, Xiaoming; Xie, Xiadan; Yang, Shengbo; Xu, Yan; Xie, Peng

    2016-01-01

    Botulinum toxin (BoNT) can relieve muscle spasticity by blocking axon terminals acetylcholine release at the motor endplate (MEP) and is the safest and most effective agent for the treatment of muscle spasticity in children with cerebral palsy. In order to achieve maximum effect with minimum effective dose of BoNT, one needs to choose an injection site as near to the MEP zone as possible. This requires a detailed understanding about the nerve terminal distributions within the muscles targeted for BoNT injection. This study focuses on BoNT treatment in children with muscle spasms caused by cerebral palsy. Considering the differences between children and adults in anatomy, we used child cadavers and measured both the nerve entry points and nerve terminal sense zones in three deep muscles of the anterior forearm: flexor digitorum profundus (FDP), flexor pollicis longus (FPL), and pronator quadratus (PQ). We measured the nerve entry points by using the forearm midline as a reference and demonstrated intramuscular nerve terminal dense zones by using a modified Sihler's nerve staining technique. The locations of the nerve entry points and that of the nerve terminal dense zones in the muscles were compared. We found that all nerve entry points are away from the corresponding intramuscular nerve terminal dense zones. Simply selecting nerve entry points as the sites for BoNT injection may not be an optimal choice for best effects in blocking muscle spasm. We propose that the location of the nerve terminal dense zones in each individual muscle should be used as the optimal target sites for BoNT injection when treating muscle spasms in children with cerebral palsy.

  8. Using family and staff experiences of a botulinum toxin-A service to improve service quality.

    Science.gov (United States)

    Burton, K L O; Bau, K; Lewis, J; Aroyan, K R; Botha, B; Botman, A G M; Stewart, K; Waugh, M-C A; Paget, S P

    2017-07-26

    The decision for families to proceed with botulinum toxin-A (BoNT-A) injections for managing childhood conditions involving hypertonia can be complex. Family-centred care is a service model that facilitates supporting families in this decision-making process. Understanding families' experiences of services is critical to developing family-centred care. The aim of this project was therefore to increase understanding of the experiences of families of children attending a BoNT-A service in order to improve the service and its family-centred approach to care. Sixteen staff of a BoNT-A service participated in a patient journey mapping exercise. Nine families of the service participated in in-depth interviews. Interviews were audio-recorded and transcribed verbatim. Data from the staff session and interviews were analysed independently using grounded, hermeneutic thematic analysis. Staff sessions revealed 5 core themes that related to impacting on the family experience. Family interviews revealed 4 core themes, with 7 subthemes and 1 latent theme. Areas of importance identified by families relating to BoNT-A treatment included acknowledgement of individual needs, care coordination, empowerment of families and patients, consistency in service delivery, and the distressing nature of appointment and decision-making. Comparison of the data from the staff patient journey mapping and family interviews suggested that staff have a good but incomplete understanding of the factors important to families, highlighting the need for consumer engagement in establishing family-centred care. The themes identified can guide the provision of family-centred BoNT-A injection clinics. © 2017 John Wiley & Sons Ltd.

  9. Advances in botulinum toxin detection method in vitro%肉毒毒素体外检测方法的研究进展

    Institute of Scientific and Technical Information of China (English)

    叶婷(综述); 张雪平(审校)

    2016-01-01

    肉毒毒素是肉毒梭状芽胞杆菌在生长繁殖过程中产生的一种神经毒素,对人和动物具有强毒性和高致死性,在世界范围内,肉毒中毒的案例时有发生,病情严重者一般2~3d即可死亡。肉毒毒素产品所用的体内检测方法(小鼠生物法)的结果变异系数大,不利于肉毒毒素产品含量的标准化控制。因而,建立准确且灵敏度高的肉毒毒素体外检测方法,在临床治疗及制品的质量控制方面都具有重要意义,现就常用的肉毒毒素体外检测方法作一阐述。%Botulinum toxin is a neurotoxin generated in the growth of the clostridium botulinum, which has an extremely tox-icity and seriously lethal effect for human and animal. Botulism cases frequently occur in the worldwide, few serious pa-tients will die in two to three days. In addition, the detection method for botulinum toxin product is carried out the mouse bioassay in vivo which has a higher coefficient of variations, so it is not conducive to the standardization of qality control for content of botulinum toxin product. Therefore, it has a great significance to set up accurate and sensitive detection methods in vitro in clinical treatment of botulism and quality control of botulinum toxin product. The paper summarizes the latest progress in detection methods for botulinum toxin in vitro.

  10. FDA Approves First Botulism Antitoxin for Use in Neutralizing All Seven Known Botulinum Nerve Toxin Serotypes

    Science.gov (United States)

    ... News & Events Home News & Events Newsroom Press Announcements FDA NEWS RELEASE For Immediate Release: March 22, 2013 ... Inquiries: Morgan Liscinsky, 301-796-0397, morgan.liscinsky@fda.hhs.gov Consumer Inquiries: 888-INFO-FDA, OCOD@ ...

  11. Identification of Small Molecules against Botulinum Neurotoxin B Binding to Neuronal Cells at Ganglioside GT1b Binding Site with Low to Moderate Affinity

    Science.gov (United States)

    2014-10-01

    Diagnosis of the National Cancer Institute for the chemicals we received from the repository. iii ABSTRACT Clostridium botulinum bacteria produce...proteins. A recombinant bivalent vaccine (rBV A/B) expressed in Pichia pastoris entered Phase III clinical trials in 2013. Currently no FDA-licensed...intoxication inhibition of botulinum neurotoxin serotype A within neurons by small-molecule, non-peptidic inhibitors. Toxins ( Basel ) 3:207-217. Schiavo, G

  12. Antibody-induced secondary treatment failure in a patient treated with botulinum toxin type A for glabellar frown lines

    Directory of Open Access Journals (Sweden)

    Stengel G

    2011-11-01

    Full Text Available Gabriele Stengel, Eva Kristina Bee Hautarztpraxis Stengel and Bee, Münster, Germany Abstract: Botulinum toxin type A (BTX-A preparations are widely used nonsurgical treatments for facial wrinkles. Higher doses of BTX-A are also used for therapeutic purposes in the treatment of conditions involving increased muscle tone, such as cervical dystonia. The phenomenon of antibody-induced treatment failure is well known in the therapeutic setting, but reports are also emerging following cosmetic use of BTX-A. We describe the case of a 41-year-old female nurse who developed secondary treatment failure during 6 years of BTX-A treatment for glabellar lines. After a good response to the first BTX-A injection, the intensity and duration of effect decreased after subsequent treatments. Antibody tests revealed a high titer of neutralizing anti-BTX-A antibodies. This case shows secondary treatment failure due to the production of neutralizing antibodies following administration of BTX-A formulations for cosmetic purposes and demonstrates that immunogenicity of BTX-A preparations is an important consideration, even in the cosmetic setting. Keywords: botulinum toxin type A, neutralizing antibodies, antibody-induced treatment failure

  13. [Bacterial ecology and resistance to antibiotics in patients with neurogenic overactive bladder treated with intravesical botulinum toxin injections].

    Science.gov (United States)

    Levy, J; Le Breton, F; Jousse, M; Haddad, R; Verollet, D; Guinet-Lacoste, A; Amarenco, G

    2014-10-01

    For the last ten years, botulinum neurotoxin type A has become the gold standard for the treatment of neurogenic overactive detrusor. Bacterial colonization is common for these patients using clean intermittent self-catheterization, and toxin injections are at risk of urinary tract infections. The aim of our study was to determine the prevalence of different germs and their resistance to antibiotics in patients with neurogenic bladder, treated with intravesical botulinum toxin injections. This epidemiologic study took place from September to October 2012 in a urodynamic and neurourology unit in a teaching hospital in Paris, France. Eighty patients with a valid urine culture according to our protocol, were included. Fourty-four culture were positive with 45 bacteria. We found an Escherichia coli in 42.5%, a Klebsiella pneumoniae in 7.5%, a Citrobacter freundii and an enterococcus in 2.5%, and a Staphylococcus aureus in 1.25%. Penicillin resistance were found in 51.11%, 3rd generation cephalosporins in 8.89%, quinolones in 28.89% and sulfamids in 24.44%. None were resistant to fosfomycin. E. coli was the most frequent bacterium. No resistance to fosfomycin was found. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Structural analysis of Clostridium botulinum neurotoxin type D as a platform for the development of targeted secretion inhibitors.

    Science.gov (United States)

    Masuyer, Geoffrey; Davies, Jonathan R; Moore, Kevin; Chaddock, John A; Ravi Acharya, K

    2015-09-01

    The botulinum neurotoxin type D is one of seven highly potent toxins produced by Clostridium botulinum which inhibit neurotransmission at cholinergic nerve terminals. A functional fragment derived from the toxin, LHn, consisting of the catalytic and translocation domains, has been heralded as a platform for the development of targeted secretion inhibitors. These secretion inhibitors are aimed at retargeting the toxin towards a specific cell type to inhibit vesicular secretion. Here we report crystal structures of LHn from serotype D at 2.3 Å, and that of SXN101959 at 3.1 Å resolution. SXN101959, a derivative that combines LHn from serotype D with a fragment of the growth hormone releasing hormone, has previously revealed promising results in inhibiting growth hormone release in pituitary somatotrophs. These structures offer for the first time insights into the translocation domain interaction with the catalytic domain in serotype D. Furthermore, structural information from small-angle X-ray scattering of LHn/D is compared among serotypes A, B, and D. Taken together, these results demonstrate the robustness of the 'LHn fold' across serotypes and its use in engineering additional polypeptide components with added functionality. Our study demonstrates the suitability of botulinum neurotoxin, and serotype D in particular, as a basis for engineering novel secretion inhibitors.

  15. Botulinum toxin-a in children with congenital spastic hemiplegia does not improve upper extremity motor-related function over rehabilitation alone: a randomized controlled trial.

    NARCIS (Netherlands)

    Rameckers, E.A.A.; Speth, L.A.; Duysens, J.E.J.; Vles, J.S.; Smits-Engelsman, B.C.M.

    2009-01-01

    BACKGROUND: Rehabilitation of the upper extremity in children with hemiplegic cerebral palsy has not been compared to the same intensity of therapy combined with injected botulinum toxin (BTX). OBJECTIVE: To measure the short-term (2 weeks) and long-term (6 and 9 months) effects of a standardized

  16. 肉毒杆菌及肉毒毒素研究进展%Progress in Research on Bacillus botulinus and Botulinum Toxins

    Institute of Scientific and Technical Information of China (English)

    赵思俊; 李雪莲; 曹旭敏; 王娟; 王玉东; 王君玮; 曲志娜

    2013-01-01

    肉毒杆菌是一种致命病菌,能引起肉毒中毒症。肉毒杆菌作为影响食品安全的一个重要风险因素,尤其是在新西兰恒天然公司部分产品受到肉毒杆菌污染事件发生后,肉毒杆菌及肉毒毒素受到了普遍关注。现就肉毒杆菌及肉毒毒素的生物学特性、中毒机制、诊断及治疗研究进展进行综述。%Bacillus botulinus is a deadly bacteria,can cause botulism disease by botulinum toxin which is among the most powerful known poisons. As an important risk factor for food safety,especially the in-cident of the product for Fonterra by botulinum toxin contamination was occured,Bacillus botulinus and botulinum toxin has been widespread concerned. The paper reviews the progress of biological characteris-tics,toxic mechanism,diagnosis and treatment for Bacillus botulinus and botulinum toxin.

  17. Kinematic aiming task: measuring functional changes in hand and arm movements after botulinum toxin-A injections in children with spastic hemiplegia.

    NARCIS (Netherlands)

    Rameckers, E.A.A.; Speth, L.A.; Duysens, J.E.J.; Vles, J.S.; Smits-Engelsman, B.C.M.

    2007-01-01

    OBJECTIVE: To describe different aspects of a kinematic aiming task (KAT) as a quantitative way to assess changes in arm movements within 2 wks after botulinum toxin-A (BTX-A) injections in children with spastic hemiplegia. DESIGN: Intervention study randomized clinical trial; follow-up within 4 wks

  18. Kinematic aiming task: measuring functional changes in hand and arm movements after botulinum toxin-A injections in children with spastic hemiplegia.

    NARCIS (Netherlands)

    Rameckers, E.A.A.; Speth, L.A.; Duysens, J.E.J.; Vles, J.S.; Smits-Engelsman, B.C.M.

    2007-01-01

    OBJECTIVE: To describe different aspects of a kinematic aiming task (KAT) as a quantitative way to assess changes in arm movements within 2 wks after botulinum toxin-A (BTX-A) injections in children with spastic hemiplegia. DESIGN: Intervention study randomized clinical trial; follow-up within 4 wks

  19. Alterations in CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H[subscript 2][superscript 15]O PET Study

    Science.gov (United States)

    Ali, S. Omar; Thomassen, Michael; Schulz, Geralyn M.; Hosey, Lara A.; Varga, Mary; Ludlow, Christy L.; Braun, Allen R.

    2006-01-01

    Speech-related changes in regional cerebral blood flow (rCBF) were measured using H[subscript 2][superscript 15]O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest…

  20. Functional effects of botulinum toxin type-A treatment and subsequent stretching of spastic calf muscles: a study in patients with hereditary spastic paraplegia

    NARCIS (Netherlands)

    Niet, M. de; Bot, S.T. de; Warrenburg, B.P.C. van de; Weerdesteijn, V.G.M.; Geurts, A.C.H.

    2015-01-01

    OBJECTIVE: Although calf muscle spasticity is often treated with botulinum toxin type-A, the effects on balance and gait are ambiguous. Hereditary spastic paraplegia is characterized by progressive spasticity and relatively mild muscle weakness of the lower limbs. It is therefore a good model to eva

  1. The combined effect of lower-limb multilevel botulinum toxin type A and comprehensive rehabilitation on mobility in children with cerebral palsy: A randomized clinical trial

    NARCIS (Netherlands)

    Scholtes, V.A.; Dallmeijer, A.J.; Knol, D.L.; Speth, L.A.; Maathuis, C.G.; Jongerius, P.H.; Becher, J.G.

    2006-01-01

    Objective: To evaluate the combined effect on mobility of treatment with multilevel botulinum toxin type A (BTX-A) and comprehensive rehabilitation in children with cerebral palsy (CP). Design: Randomized clinical trial using a multiple baseline design. The intervention group was treated 6 weeks aft

  2. The combined effect of lower-limb multilevel botulinum toxin type A and comprehensive rehabilitation on mobility in children with cerebral palsy : A randomized clinical trial

    NARCIS (Netherlands)

    Scholtes, Vanessa A.; Dallmeijer, Annet J.; Knol, Dirk L.; Speth, Lucianne A.; Maathuis, Carel G.; Jongerius, Peter H.; Becher, Jules G.

    2006-01-01

    Objective: To evaluate the combined effect on mobility of treatment with multilevel botulinum toxin type A (BTX-A) and comprehensive rehabilitation in children with cerebral palsy (CP). Design: Randomized clinical trial using a multiple baseline design. The intervention group was treated 6 weeks aft

  3. Effects of leg muscle botulinum toxin A injections on walking in children with spasticity-related cerebral palsy: a systematic review.

    NARCIS (Netherlands)

    Ryll, U.; Bastiaenen, C.; Bie, R. de; Staal, B.

    2011-01-01

    AIM: To assess treatment effects of botulinum toxin type A (BoNT-A) on walking of children with leg spasticity due to cerebral palsy (CP) compared with usual care. METHOD: We systematically searched the databases CINAHL, Cochrane, PEDro, EMBASE, and PubMed from July 1993 until July 2009 and addition

  4. Feasibility of a Day-Camp Model of Modified Constraint-Induced Movement Therapy with and without Botulinum Toxin A Injection for Children with Hemiplegia

    Science.gov (United States)

    Eliasson, Ann-Christin; Shaw, Karin; Ponten, Eva; Boyd, Roslyn; Krumlinde-Sundholm, Lena

    2009-01-01

    The objective of the study was to investigate the feasibility of modified constraint-induced (CI) therapy provided in a 2-week day-camp model with and without intramuscular botulinum toxin type A (BoNT-A) injections for children with congenital cerebral palsy. Sixteen children with congenital hemiplegia, Manual Ability Classification System (MACS)…

  5. The Profile of Patients and Current Practice of Treatment of Upper Limb Muscle Spasticity with Botulinum Toxin Type A: An International Survey

    Science.gov (United States)

    Bakheit, Abdel Magid

    2010-01-01

    To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31…

  6. Src Family Kinase Inhibitors Antagonize the Toxicity of Multiple Serotypes of Botulinum Neurotoxin in Human Embryonic Stem Cell-Derived Motor Neurons

    Science.gov (United States)

    Burnett, James C.; Nuss, Jonathan E.; Wanner, Laura M.; Peyser, Brian D.; Du, Hao T.; Gomba, Glenn Y.; Kota, Krishna P.; Panchal, Rekha G.; Gussio, Rick; Kane, Christopher D.; Tessarollo, Lino

    2015-01-01

    Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of BoNT intoxication in human motor neurons, focusing on Src family kinase (SFK) signaling. Motor neurons derived from human embryonic stem (hES) cells were treated with a panel of SFK inhibitors and intoxicated with BoNT serotypes A, B, or E (which are responsible for >95 % of human botulism cases). Subsequently, it was found that bosutinib, dasatinib, KX2-391, PP1, PP2, Src inhibitor-1, and SU6656 significantly antagonized all three of the serotypes. Furthermore, the data indicated that the treatment of hES-derived motor neurons with multiple SFK inhibitors increased the antagonistic effect synergistically. Mechanistically, the small molecules appear to inhibit BoNTs by targeting host pathways necessary for intoxication and not by directly inhibiting the toxins’ proteolytic activity. Importantly, the identified inhibitors are all well-studied with some in clinical trials while others are FDA-approved drugs. Overall, this study emphasizes the importance of targeting host neuronal pathways, rather than the toxin’s enzymatic components, to antagonize multiple BoNT serotypes in motor neurons. PMID:25782580

  7. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    Directory of Open Access Journals (Sweden)

    Domenico Intiso

    2015-06-01

    Full Text Available Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders

  8. Efficacy and safety of botulinum toxin in treatment of anismus: A systematic review

    Institute of Scientific and Technical Information of China (English)

    Sameh Hany Emile; Hossam Ayman Elfeki; Hosam Ghazy Elbanna; Mohamed Youssef; Waleed Thabet; Tito M Abd El-Hamed; Basem Said; Ahmed Lotfy

    2016-01-01

    AIM: To evaluate the efficacy and safety of botulinum toxin type A(BTX-A) in the management of patients with anismus. METHODS: An organized search of published literature was conducted using electronic databases including: Pub Med/MEDLINE, and Cochrane Central Register of Control ed Trials, also an internet-based search using "Google Scholar" service was conducted. Both comparative and observational studies were included. We excluded irrelevant articles, editorials, case reports, reviews, and meta-analyses. The studies that followed the patients less than 6 mo were excluded. Variables collected were demographic data of the patients, technique of BTX-A injection and number of sessions, short-term and longterm clinical improvement, post-injection changes in electromyography(EMG), defecography, manometry, and balloon expulsion test, and complications recorded after BTX-A injection.RESULTS: Seven studies comprising 189 patients were included in the review. The median age of the patients was 41.2 years and female-to-male ratio was 1.3:1. The median dose of BTX-A injected per procedure was 100 IU(range, 20-100 IU). Lateral injection was done in five trails and combined lateral and posterior injections in two trials. Three studies used endorectal ultrasonographyguided technique, one study used EMG-guided technique,whereas the remaining three studies used manual palpation with the index finger. The median percentage of patients who reported initial improvement of symptoms was 77.4%(range 37.5%-86.7%), this percentage declined to a median of 46%(range 25%-100%) at 4 mo after injection of BTX-A. Rates of improvement evaluated by balloon expulsion test, EMG, and defecography ranged between(37.5%-80%),(54%-86.7%), and(25%-86.6%), respectively. Fourteen(7.4%) patients developed complications after injection of BTX-A. Complication rates across the studies ranged from 0% to 22.6%. CONCLUSION: Initial satisfactory improvement of symptoms after BTX-A injection remarkably

  9. Beneficial effects of botulinum toxin type A in trigeminal neuralgia Beneficio de la toxina botulínica tipo A en neuralgia del trigemino

    Directory of Open Access Journals (Sweden)

    Carlos Zúñiga

    2008-09-01

    Full Text Available Botulinum toxin has been thoroughly studied as a potential tool in the treatment of several pain syndromes. Therefore, we assessed the clinical effects of botulinum toxin type A injections in 12 patients with otherwise unresponsive idiopathic trigeminal neuralgia. Patients were infiltrated with 20-50 units of botulinum toxin in trigger zones. Those who presented with mandibular involvement were also infiltrated in the masseter muscle. The patients were assessed on a weekly basis using the Visual Analogic Scale for pain. Ten of our patients reported a significant benefit from botulinum toxin injections, with reduction or even disappearance of pain, and remained pain free for as long as 60 days. Our findings suggest that botulinum toxin may represent a useful therapeutic tool in the management of patients with this entity.La toxina botulínica ha sido estudiada en forma exhaustiva como una potencial herramienta en el tratamiento de múltiples síndromes dolorosos. Por lo tanto, evaluamos los efectos clínicos de la aplicación de toxina botulínica tipo A en 12 sujetos con neuralgia trigeminal idiopática resistente a manejo farmacológico. Se aplicaron en dichos sujetos entre 20 y 50 unidades de toxina botulínica tipo A en las zonas gatillo. Además se infiltró el músculo masetero en aquellos que presentaban involucro mandibular. Los sujetos fueron evaluados semanalmente con una escala visual análoga para dolor. Diez de los sujetos reportaron un beneficio significativo con el uso de toxina botulínica, con reducción e incluso desaparición del dolor, permaneciendo libres de dolor por un periodo de hasta 60 días. Nuestros hallazgos sugieren que la toxina botulínica puede representar una herramienta terapéutica útil en el manejo de pacientes con esta entidad.

  10. Differences between objective efficacy and perceived efficacy in patients with palmar hyperhidrosis treated with either botulinum toxin or endoscopic thoracic sympathectomy.

    Science.gov (United States)

    Alvarez, M A; Ruano, J; Gómez, F J; Casas, E; Baamonde, C; Salvatierra, A; Moreno, J C

    2013-03-01

    Moderate to severe palmar hyperhidrosis can disturb people's work and social and emotional lives. Botulinum toxin and sympathectomy are currently considered the most effective treatment options but few studies have analysed the concordance between efficacy and patient satisfaction in comparisons of these two types of treatments. To assess the relation between efficacy and the satisfaction of patients with palmar hyperhidrosis treated with either botulinum toxin or endoscopic thoracic sympathectomy. This retrospective, observational study included all patients treated with either botulinum toxin or endoscopic thoracic sympathectomy in a single reference hospital in 2005-2010. Information was obtained from computerized medical records and a telephone survey about patients' educational and socio-economic level, awareness of treatment options, pre- and post-treatment severity of palmar hyperhidrosis, satisfaction and associated side effects. Predictors of efficacy and patient satisfaction with each treatment were analysed with ordinal and multinomial logistic regression models. Patients who underwent sympathectomy had more severe palmar hyperhidrosis but efficacy and patient satisfaction were greater compared with patients given botulinum toxin. The severity of the compensatory palmar hyperhidrosis was predictive of less satisfaction after sympathectomy. In the group treated with botulinum toxin, low socio-economic status, lack of information about treatment options, fewer sessions and a shorter anhidrotic effect were associated with less satisfaction. In studies of expectations regarding the outcome of palmar hyperhidrosis treatment, doctors should consider the factors that determine patient satisfaction in relation to the treatment options. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  11. A case report of the beneficial effects of botulinum toxin type A on Raynaud phenomenon in a patient with lung cancer

    Science.gov (United States)

    Wang, Lu; Lei, Qi-song; Liu, Yu-ying; Song, Guan-jie; Song, Chun-ling

    2016-01-01

    Abstract Objective: Raynaud phenomenon is a vasospastic disorder affecting the hands and feet, and the efficacies of traditional treatments, such as pharmacological therapies and sympathectomy, are not uniform. Patients with paraneoplastic Raynaud phenomenon do not benefit from the traditional treatments. The use of botulinum toxin type A (BTX-A) for Raynaud phenomenon has been reported for several years; however, there are few reports regarding botulinum toxin type A in the treatment of paraneoplastic Raynaud phenomenon. We describe a case report of the beneficial effects of botulinum toxin type A on Raynaud phenomenon in a patient with lung cancer. Methods: A 63-year-old male complained of pain and discoloration of his fingers and indicated that oral nifedipine and low-dose aspirin were not effective. After approximately 8 months, he was diagnosed with lung cancer. Chemotherapy partially reduced the pain and discoloration of his fingers; however, no significant changes occurred in his fingers after the fourth cycle. We used BTX-A to treat this patient with paraneoplastic RP. A visual analogue scale (VAS) was used to assess the clinical response. Results: After approximately 2 months, the patient reported relief from pain, stiffness, numbness, and cold sensation. Furthermore, no local or general adverse effects were exhibited by the patient. Conclusion: This study used botulinum toxin type A for a patient with paraneoplastic Raynaud phenomenon. Botulinum toxin type A significantly improved the patient's clinical symptoms without significant complications. These findings suggest that BTX-A may represent a good option for the treatment of paraneoplastic RP. PMID:27749585

  12. Inhibition of botulinum toxin's association with rat brain synaptosomes by toosendanin,an antibotulismic triterpenoid

    Institute of Scientific and Technical Information of China (English)

    Jianying Zhou; Yuliang Shi

    2006-01-01

    BACKGROUND:Toosendanin(TSN),a triterpenoid derivative extracted from the bark of Melia toosendanin Sieb et Zucc,has been demonstrated to be an effective drug for treatment of experimental botulism.OBJECTIVE:To explore its antibotulismic mechanism by observing the effect of toosendanin on association of botulinum toxin(BoTx)with rat brain synaptosomes under different conditions.DESIGN:A randomized controlled experiment.SETTING:Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences.MATERIALS:Sprague-Dawley rats,weighing(220±12)g,were involved.TSN was a sample recrystallized in ethanol with a purity>98%.BoTx/A and BoTx/C of 500 ku(1.8x107mouse LD50/mg)were purchased from Wako(Japan),Horse antitoxins to BoTx/A and/C(pdmary antibodies)were purchased from Lanzhou Institute of Biological Products(China).METHODS:Major experiments were finished between March 2005 and October 2005 in key laboratory of neurobiology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences.①Preparation of synaptosome of rats:one aliquot of synaptosome was pre-incubated with TSN(17μmol/L)for 20 minutes at 4℃or 37℃(another aliquot of synaptosome which was untouched was used as control).Then,BoTx was respectively added for another 20-minute incubation.②A homochronous experiment was still Derformed at 37℃.Differently,high level of K+ was used to stimulate synaptosome for 25 minutee.Two aliquots of synaptosomes with or without TSN(17 μmol/L)were preincubated for 15 minutes.Then,30 mmol/L KCl was separately added in two aliquots,5 minutes later,13 nmol/L BoTx/C was separately added followed by 20-minute incubation.[3]The effect of TSN on BoTx binding was observed by Western blot and synchronization method.③ttest was used for comparing the difference of measurement data.MAIN OUTCOME MEASURES:The gray value of BoTx bands from westem blot was used to estimate the bound amount of BoTx.RESULTS:①Preincubation of synaptosomes with TSN(17 μmol/L)at 4

  13. Botulinum toxin-A-induced protective ptosis in the treatment of lagophthalmos associated with facial paralysis.

    Science.gov (United States)

    Yücel, Ozlem Eşki; Artürk, Nurşen

    2012-01-01

    To evaluate the safety and efficacy of the protective ptosis created by botulinum neurotoxin type-A in lagophthalmos cases due to peripheral facial paralysis. Protective ptosis was induced by 7.5 U botulinum neurotoxin type-A injection into levator muscles in 15 patients with peripheral facial paralysis and lagophthalmos. Its efficacy and safety were evaluated prospectively. Complete ophthalmological examinations were performed before and after injections; interpalpebral fissure, upper eyelid margin reflex distance, and levator muscle function were measured. In control visits, degree and duration of ptosis and side effects of the drug were evaluated. The mean age of the patients was 55 ± 14.28 years (22-78 years). Ptosis created by botulinum neurotoxin type-A injection was severe in 12 patients (80%), moderate in 2 patients (13.3%), and mild in 1 patient (6.7%). The effect of botulinum neurotoxin type-A began in 2.33 ± 1.44 days and peaked in 5.73 ± 2.63 days. No patient needed a second injection. The mean duration for ptosis was 10.53 ± 2.89 weeks. After development of ptosis, statistically significant improvement in corneal symptoms (p lagophthalmos, protective ptosis created by botulinum neurotoxin type-A injection into the levator muscle is a reliable and effective technique for the protection of the ocular surface and treatment of existing corneal complications. It represents an alternative treatment modality in cases requiring surgery.

  14. Effect of Fill Temperature on Clostridium botulinum Type A Toxin Activity during the Hot Filling of Juice Bottles.

    Science.gov (United States)

    Skinner, Guy E; Fleischman, Gregory J; Balster, Fran; Reineke, Karl; Reddy, N Rukma; Larkin, John W

    2015-08-01

    The potential threat of terrorist attacks against the United States food supply using neurotoxin produced by Clostridium botulinum (BoNT) has resulted in the need for studying the effect of various food process operations on the bioavailability of this toxin. The objective of this study was to evaluate C. botulinum type A neurotoxin bioavailability after a simulated hot fill juice bottling operation. C. botulinum type A acid mud toxin (∼10(6) mouse lethal dose [MLD50]/ml) was deposited into juice bottles at an experimentally determined fastest cooling spot. Bottles (12 or 20 oz [355 and 592 ml]) were filled with either apple juice or an orange drink, at 80 or 85°C, in either upright or inverted orientations. Toxicity of the juice was evaluated as a function of holding time (1 to 2 min) by the mouse bioassay. The fastest cooling point in the upright orientation was determined to be at a bottle's bottom rim. In the inverted orientation, the fastest cooling point was in the bottle cap region. With respect to these two points, the upright bottle cooled faster than the inverted bottle, which was reflected in a higher inactivation of BoNT in the latter. For the orange drink (pH 2.9) toxicity was reduced by 0.5 × 10(6) MLD50/ml to a nondetectable level after 1 min in all bottle sizes, orientations, and temperatures as measured by the mouse bioassay. This indicates that there was at least a 0.5 × 10(6) MLD50/ml reduction in activity. Inactivation in apple juice (pH 4.0), to the same degree as in the orange drink, was found only for the inverted orientation at 85°C. Complete inactivation in apple juice for all conditions was found at a lower added toxin level of 0.25 × 10(5) MLD50/ml. In general, bottle inversion and filling at 85°C provided complete inactivation of BoNT to the 0.5 × 10(6) MLD50/ml level. All experiments resulted in the inactivation of 2.5 × 10(4) MLD50/ml of BoNT regardless of juice type, fill temperature, or bottle orientation and size.

  15. Toxina botulínica y su empleo en la patología oral y maxilofacial Botulinum toxin and its use in oral and maxillofacial pathology

    Directory of Open Access Journals (Sweden)

    D. Martínez-Pérez

    2004-06-01

    Full Text Available Resumen: Las toxinas botulínicas son exotoxinas de la bacteria formadora de esporas Clostridim botulinum y los agentes causantes del botulismo. Cuando se inyecta en el músculo produce una parálisis flácida. El efecto clínico está directamente relacionado con la dosis y debe ajustarse para cada caso concreto. La Toxina botulínica ha demostrado en los más de veinte años en que se está utilizando que es un fármaco seguro. Las indicaciones de la toxina botulínica en la actualidad incluyen todas aquellas patologías que resultan de la hiperfunción muscular y la disfunción autonómica.Abstract: Botilinum toxins are exotoxins of the bacteria that form the Clostridium botulinum spores and the causative agents of botulism. When injected into the muscle flaccid paralysis is produced. The clinical effect is directly related with the dose and is should be adjusted for each particular case. over the last twenty years that it has been in use, the botulinum toxin has shown itself to be a reliable drug. Current indications for the use of botulinum toxin include all those pathologies which are the results of muscle hyperfunction and autonomic dysfunction.

  16. Universal and specific quantitative detection of botulinum neurotoxin genes

    Directory of Open Access Journals (Sweden)

    Arnon Stephen S

    2010-10-01

    Full Text Available Abstract Background Clostridium botulinum, an obligate anaerobic spore-forming bacterium, produces seven antigenic variants of botulinum toxin that are distinguished serologically and termed "serotypes". Botulinum toxin blocks the release of acetylcholine at neuromuscular junctions resulting in flaccid paralysis. The potential lethality of the disease warrants a fast and accurate means of diagnosing suspected instances of food contamination or human intoxication. Currently, the Food and Drug Administration (FDA-accepted assay to detect and type botulinum neurotoxins (BoNTs is the mouse protection bioassay. While specific and sensitive, this assay requires the use of laboratory animals, may take up to four days to achieve a diagnosis, and is unsuitable for high-throughput analysis. We report here a two-step PCR assay that identifies all toxin types, that achieves the specificity of the mouse bioassay while surpassing it in equivalent sensitivity, that has capability for high-throughput analysis, and that provides quantitative results within hours. The first step of our assay consists of a conventional PCR that detects the presence of C. botulinum regardless of the neurotoxin type. The second step uses quantitative PCR (qPCR technology to determine the specific serotype of the neurotoxin. Results We assayed purified C. botulinum DNA and crude toxin preparations, as well as food and stool from healthy individuals spiked with purified BoNT DNA, and one stool sample from a case of infant botulism for the presence of the NTNH gene, which is part of the BoNT gene cluster, and for the presence of serotype-specific BoNT genes. The PCR surpassed the mouse bioassay both in specificity and sensitivity, detecting positive signals in BoNT preparations containing well below the 1 LD50 required for detection via the mouse bioassay. These results were type-specific and we were reliably able to quantify as few as 10 genomic copies. Conclusions While other studies

  17. Prevalence of Bleeding Complications Following Ultrasound-Guided Botulinum Toxin Injections in Patients on Anticoagulation or Antiplatelet Therapy.

    Science.gov (United States)

    LaVallee, Jeffrey; Royer, Regan; Smith, Geoffrey

    2017-06-16

    Patients on anticoagulation or antiplatelet therapy may be at higher risk for bleeding complications following intramuscular chemodenervation injections. Musculoskeletal ultrasound may be able to reduce the risk of bleeding complications by providing real-time visualization of vascular structures and postinjection monitoring. Limited data exist addressing the risk of bleeding complications following ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures in the setting of anticoagulation or antiplatelet therapy. To provide initial outcome data regarding bleeding complications in patients on anticoagulation or antiplatelet therapy who have received ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures. Retrospective, medical record review. Academic institution outpatient spasticity clinic. Total of 328 ultrasound-guided intramuscular botulinum toxin injections performed in 15 patients (mean age 53.8 years) with the predominant indication for chemodenervation being spastic paresis secondary to stroke. The medical records of all patients receiving ultrasound-guided intramuscular chemodenervation procedures performed between July 1, 2011, and October 16, 2015, were reviewed for demographic information, details regarding anticoagulation therapy, procedure specifics, and postinjection bleeding complications. All patients had a postinjection ultrasound to screen for hematoma. Prevalence of clinically significant bleeding complications and of sonographically documented subclinical bleeding complications following ultrasound-guided chemodenervation procedures in patients on anticoagulation or antiplatelet therapy. Of 328 procedures, only 2 subclinical hematomas were detected, resulting in a bleeding complication rate of 0.61% in this patient population. The target muscles in these cases were tibialis posterior and pronator teres, and both cases were in patients on anticoagulation therapy (as opposed to antiplatelet

  18. Renewable Surface Fluorescence Sandwich Immunoassay Biosensor for Rapid Sensitive Botulinum Toxin Detection in an Automated Fluidic Format

    Energy Technology Data Exchange (ETDEWEB)

    Grate, Jay W.; Warner, Marvin G.; Ozanich, Richard M.; Miller, Keith D.; Colburn, Heather A.; Dockendorff, Brian P.; Antolick, Kathryn C.; Anheier, Norman C.; Lind, Michael A.; Lou, Jianlong; Marks, James D.; Bruckner-Lea, Cindy J.

    2009-03-05

    A renewable surface biosensor for rapid detection of botulinum toxin is described based on fluidic automation of a fluorescence sandwich immunoassay, using a recombinant fragment of the toxin heavy chain as a structurally valid simulant. Monoclonal antibodies AR4 and RAZ1 bind to separate epitopes of both this fragment and the holotoxin. The AR4 antibody was covalently bound to Sepharose beads and used as the capture antibody. A rotating rod flow cell was used to capture these beads delivered as a suspension by the sequential injection flow system, creating a 3.6 microliter column. After perfusing the bead column with sample and washing away the matrix, the column was perfused with Alexa 647 dye-labeled RAZ1 antibody as the reporter. Optical fibers coupled to the rotating rod flow cell at a 90 degree angle to one another delivered excitation light from a HeNe laser and collected fluorescent emission light for detection. After each measurement, the used sepharose beads are released and replaced with fresh beads. In a rapid screening approach to sample analysis, the toxin simulant was detected to concentrations of 10 pM in less than 20 minutes.

  19. Pré-compostagem de cadáveres de bovinos acometidos pelo botulismo The effect of composting cattle carcasses on botulinum spores and toxin content

    Directory of Open Access Journals (Sweden)

    Vera C.L.M. Curci

    2007-04-01

    of botulinum toxin. The diagnosis of botulinum poisoning was based on clinical and pathological, epidemic and/or laboratorial characteristics. Of the five bovines with clinical signs of chronic botulism, three were affected by the type D toxin, one by the CD complex, and one was negative for toxin and spores of C. botulinum in the viscera using a mouse bioassay. The composting process was carried out in beds with carcasses cut up and mixed with sawdust as a carbon source. They were kept anaerobic under a plastic sheet for 50 days. The temperature of the beds was monitored during the period and oscillated from 40.5 to 52.4ºC. After this time, soft tissue had complete decomposed with a significant loss of weight (26.5-44.5%. The remaining bones no longer contained spores or botulinum toxin in the 5 samples taken from each carcass. Only 2 of the 200 samples of homogenized remaining (40 for each carcass contained spores of C. botulinum type C. All samples were negative for botulinum toxin using the mouse bioassay. Composting carcasses of cattle that died from botulism eliminated botulinum spores and toxin from the remains.

  20. The therapeutic usage of botulinum toxin (Botox in non-cosmetic head and neck conditions – An evidence based review

    Directory of Open Access Journals (Sweden)

    Kamran Habib Awan

    2017-01-01

    Full Text Available Botulinum toxin (Botox is an exotoxin produced from Clostridium botulinum. It blocks the release of acetylcholine from the cholinergic nerve end plates resulting in inactivity of the muscles or glands innervated. The efficacy of Botox in facial aesthetics is well established; however, recent literature has highlighted its utilization in multiple non-cosmetic medical and surgical conditions. The present article reviews the current evidence pertaining to Botox use in the non-cosmetic head and neck conditions. A literature search was conducted using MEDLINE, EMBASE, ISI Web of Science and the Cochrane databases limited to English Language articles published from January 1980 to December 2014. The findings showed that there is level 1 evidence supporting the efficacy of Botox in the treatment of laryngeal dystonia, headache, cervical dystonia, masticatory myalgia, sialorrhoea, temporomandibular joint disorders, bruxism, blepharospasm, hemifacial spasm and rhinitis. For chronic neck pain there is level 1 evidence to show that Botox is ineffective. Level 2 evidence exists for vocal tics and trigeminal. For stuttering, facial nerve paresis, Frey’s syndrome and oromandibular dystonia the evidence is level 4. Thus, there is compelling evidence in the published literature to demonstrate the beneficial role of Botox in a wide range of non-cosmetic conditions pertaining to the head and neck (mainly level 1 evidence. With more and more research, the range of clinical applications and number of individuals getting Botox will doubtlessly increase. Botox appears to justify its title as ‘the poison that heals’.

  1. Obesity Treatment with Botulinum Toxin-A Is Not Effective: a Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Bustamante, Fabio; Brunaldi, Vitor Ottoboni; Bernardo, Wanderley Marques; de Moura, Diogo Turiani H; de Moura, Eduardo Turiani H; Galvão, Manoel; Santo, Marco Aurélio; de Moura, Eduardo Guimarães H

    2017-08-15

    The effectiveness of gastric injections of botulinum toxin-A (BTA) as primary treatment for obesity is not well known since results in literature are discrepant. Hence, we aimed to systematically review and meta-analyze the available data to assess the real effect of BTA therapy. We searched MEDLINE, Embase, Cochrane, SCOPUS, EBSCO, LILACS, and BVS. We considered eligible only randomized controlled trials enrolling obese patients comparing BTA versus saline injections. Our initial search identified 8811 records. Six studies fulfilled eligibility criteria. After critical appraisal, two articles were excluded and we meta-analyzed the remainder. The mean difference for absolute weight loss and BMI reduction were 0.12 [CI 95%, - 1.14, 1.38] and - 0.06 [95% CI, - 0.92, 0.81], respectively. Therefore, we concluded that treatment of obesity with BTA is not effective.

  2. Outcomes of Botulinum Toxin Type A Injection Followed by Rehabilitation in Cases of Cerebral Palsy With Upper Extremity Involvement.

    Science.gov (United States)

    Karaca, Burcu; Ünlü, Ece; Köse, Gülşen; Gönen, Emel; Çakcı, Aytül

    2016-03-01

    We evaluated the efficiency of botulinum toxin type A injection followed by a rehabilitation program including individual therapy, group therapy, and occupational therapy in cases of cerebral palsy with upper extremity involvement. A total of 29 injections were performed on 25 patients, and the patients were placed on rehabilitation program. At 3-month and 6-month assessments, there was a significant improvement in lateral grip strength, 9 Hole Peg test, Upper Limb Physician's Rating Scale and pediatric functional independence measure total scores. There were significant decreases in active range of motion in elbow extension, supination, and wrist extension, and Modified Ashworth Scale in elbow flexion, elbow pronation, and wrist flexion at 6-week, 3-month, and 6-month assessments. Combination of group therapy with traditional therapy methods after injection is effective in cases of cerebral palsy with upper extremity involvement.

  3. Botulinum toxin in severe upper extremity spasticity among patients with traumatic brain injury: an open-labeled trial.

    Science.gov (United States)

    Yablon, S A; Agana, B T; Ivanhoe, C B; Boake, C

    1996-10-01

    We studied the effect of botulinum toxin A (BTXA) among patients with traumatic brain injury (TBI) and severe spasticity unresponsive to conservative management. Twenty-one consecutive adult patients with severe spasticity involving the wrist and finger flexor musculature were treated with BTXA injection (20 to 40 units per muscle) under EMG guidance. After injection, patients received passive range of motion (ROM) exercise, with modalities and casting as clinically indicated. Outcome measures, including wrist ROM and the modified Ashworth Scale (MAS), were assessed 2 to 4 weeks after injection. Among the respective acute and chronic groups, mean ROM improved 42.9 (p = 0.001) and 36.2 degrees (p < 0.001). Mean MAS rating improved 1.5 (p = 0.01) and 1.47 (p = 0.002) points. There were no significant adverse effects. BTXA, in conjunction with conventional modalities, significantly improves spasticity and ROM in the distal upper extremity musculature of patients with TBI.

  4. A literature review on the efficacy and safety of botulinum toxin: An injection in post-stroke spasticity

    Directory of Open Access Journals (Sweden)

    Majid Ghasemi

    2013-01-01

    Full Text Available Background: A variety of techniques for the management of spasticity have been suggested, including positioning, cryotherapy, splinting and casting, biofeedback, electrical stimulation, and medical management by pharmacological agents, Botulinum toxin A (BTA is now the pharmacological treatment of choice in focal spasticity. BTA by blocking acetylcholine release at neuromuscular junctions accounts for its therapeutic action to relieve spasticity. Methods: A computerized search of Pub Med was carried out to find the latest result about efficacy of BTA in management of post stroke spasticity. Result: Among 84 articles were found, frothy of them included in this review and divided to lower and upper extremity. Conclusions: BTA is a treatment choice in reducing tone and managing post stroke spasticity .

  5. Technique for iliopsoas ultrasound-guided active electromyography-directed botulinum a toxin injection in cerebral palsy.

    Science.gov (United States)

    Willenborg, Michael J; Shilt, Jeffrey S; Smith, Beth Paterson; Estrada, Roquel L; Castle, Jason A; Koman, L Andrew

    2002-01-01

    Symptomatic hip flexion deformity secondary to iliopsoas spasticity may interfere with gait, impair sitting balance, or contribute to hip subluxation or dislocation. A nonsurgical, minimally invasive technique to ameliorate iliopsoas spasticity is presented. The technique uses intramuscular injections of botulinum A toxin to provide selective neuromuscular blockade of the iliacus or psoas muscles or both. Because of the anatomic location of the target muscles, this technique uses ultrasound guidance for needle placement. Active electromyographic stimulation is used to verify the needle position adjacent to active myoneural interfaces. The authors' experience to date includes the treatment of 28 patients (53 hips). Use of this technique has resulted in improved hip range of motion. No intraoperative or postoperative adverse events or complications have been observed.

  6. Effects of botulinum toxin type A for spastic foot in post-stroke patients enrolled in a rehabilitation program

    Directory of Open Access Journals (Sweden)

    Leonardo Halley Carvalho Pimentel

    2014-01-01

    Full Text Available The objective of this study was to evaluate the effects of botulinum toxin type A (BTX-A on spastic foot in stroke patients in a rehabilitation program. Method: Hemiparetic stroke patients (n=21 enrolled in a rehabilitation program were divided into two groups. The first group (n=11 received a total of 300UI BTX-A, and the second group (n=10 received 100 UI BTX-A. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for Modified Ashworth Score, time walking 10 meters, and the Functional Independence Measure (mFIM motor score. Results: The higher-dose group exhibited a significant improvement in spasticity, and both groups showed an improvement in time walking 10 meters and mFIM, with no significant differences between them. Conclusions: Our findings suggest that gains in gait velocity and functional independence were not correlated to BTX-A dose.

  7. Quantitative Effects on Proximal Joints of Botulinum Toxin Treatment for Gastrocnemius Spasticity: A 4-Year-Old Case Study

    Directory of Open Access Journals (Sweden)

    Veronica Cimolin

    2009-01-01

    Full Text Available Botulinum toxin A (BTA is a recognized treatment for the early management of spasticity in children with Cerebral Palsy. This study quantified with Gait Analysis (GA the gait pattern of a 4-year-old diplegic child with calf contracture before, 5 days, and 3 months after BTA injections into gastrocnemius. Kinematic and kinetic data of main lower limb joints were investigated. After only 5 days, ankle dorsi-plantarflexion and knee flex-extension improved, but hip joint worsened, increasing its excessive flexion, to compensate the improvement in knee position of the treated limb and to obtain better stability. A worsening of hip power happened. After 3 months, all joints generally improved their position during gait cycle. Hip and knee joints increased their range of movement and improvements occurred at ankle kinematics and kinetisc, too; a better ankle position and an increase of its capacity of propulsion during terminal stance were evident.

  8. An in vivo analysis of facial muscle change treated with botulinum toxin type A using digital image speckle correlation

    Science.gov (United States)

    Xu, Yan; Palmaccio, Samantha Palmaccio; Bui, Duc; Dagum, Alexander; Rafailovich, Miriam

    Been famous for clinical use from early 1980s, the neuromuscular blocking agent Botulinum toxin type A (BTX-A), has been used to reduce wrinkles for a long time. Only little research has been done to quantify the change of muscle contraction before and after injection and most research paper depend on subjective evaluation from both patients and surgeons. In our research, Digital Image Speckle Correlation (DISC) was employed to study the mechanical properties of skin, contraction mode of muscles (injected) and reaction of neighbor muscle group (un-injected).At the same time, displacement patterns (vector maps)generated by DISC can predict injection locus for surgeons who normally handle it depending only on visual observation.

  9. Effects of Botulinum Toxin on Jaw Motor Events during Sleep in Sleep Bruxism Patients: A Polysomnographic Evaluation

    Science.gov (United States)

    Shim, Young Joo; Lee, Moon Kyu; Kato, Takafumi; Park, Hyung Uk; Heo, Kyoung; Kim, Seong Taek

    2014-01-01

    Study Objectives: To investigate the effects of botulinum toxin type A (BoNT-A) injection on jaw motor episodes during sleep in patients with or without orofacial pain who did not respond to oral splint treatment. Methods: Twenty subjects with a clinical diagnosis of SB completed this study. Ten subjects received bilateral BoNT-A injections (25 U per muscle) into the masseter muscles only (group A), and the other 10 received the injections into both the masseter and temporalis muscles (group B). Video-polysomnographic (vPSG) recordings were made before and at 4 weeks after injection. Rhythmic masticatory muscle activity (RMMA) and orofacial activity (OFA) were scored and analyzed for several parameters (e.g., frequency of episodes, bursts per episode, episode duration). The peak amplitude of electromyographic (EMG) activity in the two muscles was also measured. Results: BoNT-A injection did not reduce the frequency, number of bursts, or duration for RMMA episodes in the two groups. The injection decreased the peak amplitude of EMG burst of RMMA episodes in the injected muscles (p < 0.001, repeated measure ANOVA) in both groups. At 4 weeks after injection, 9 subjects self-reported reduction of tooth grinding and 18 subjects self-reported reduction of morning jaw stiffness. Conclusions: A single BoNT-A injection is an effective strategy for controlling SB for at least a month. It reduces the intensity rather than the generation of the contraction in jaw-closing muscles. Future investigations on the efficacy and safety in larger samples over a longer follow-up period are needed before establishing management strategies for SB with BoNT-A. Citation: Shim YJ; Lee MK; Kato T; Park HU; Heo K; Kim ST. Effects of botulinum toxin on jaw motor events during sleep in sleep bruxism patients: a polysomnographic evaluation. J Clin Sleep Med 2014;10(3):291-298. PMID:24634627

  10. Influence of botulinum toxin on rabbit jaw muscle activity and anatomy

    NARCIS (Netherlands)

    Korfage, J.A.M.; Wang, J.; Lie, S.H.J.T.J.; Langenbach, G.E.J.

    2012-01-01

    Introduction: Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Methods: Three months after the injection of botulinum

  11. Botulinum toxin effect on salivary flow rate in children with cerebral palsy.

    NARCIS (Netherlands)

    Jongerius, P.H.; Rotteveel, J.J.; Limbeek, J. van; Gabreëls, F.J.M.; Hulst, K. van; Hoogen, F.J.A. van den

    2004-01-01

    OBJECTIVE: To investigate the effectiveness of botulinum neurotoxin (BoNT) type A in reducing salivary flow rate in children with cerebral palsy (CP) with severe drooling. METHODS: During a controlled clinical trial, single-dose BoNT injections into the submandibular salivary glands were compared wi

  12. C型肉毒梭菌肉毒毒素的提取与鉴定%Extraction and Identification of Botulinum Toxins

    Institute of Scientific and Technical Information of China (English)

    薛正坤; 吴伟; 张晶; 李超毅; 吴辉; 李莲瑞

    2013-01-01

    [目的]通过对C型肉毒梭菌肉毒毒素的提取与鉴定,为类毒素和抗毒素的制备及抗原性分析奠定基础.[方法]将分离鉴定得到的C型肉毒梭菌通过扩大培养、产毒培养后将产生的肉毒毒素采用除菌过滤、硫酸铵盐盐析、离心、透析、浓缩的方法从产毒培养基中分离提取出来.再将提取的肉毒毒素通过SDS-PAGE鉴定毒素蛋白的分子量.[结果]分离出来的毒素蛋白重链和轻链分别在98和53 KDa左右,与C型肉毒毒素的理论分子量相符.[结论]提取的肉毒毒素是C型肉毒毒素.%[Objective] The project aims to lay a foundation for the preparation and antigenicity analysis of the toxoid and antitoxic through extraction and identification of the type C clostridium botulinumn. [Method] The separated and identified type C clostridium botulinum underwent expanding training, and after that, the procreant poison produced botulinum toxin through such methods as the aseptic filtration, ammonium sulfate salting separation, centrifugal treatment, dialysis and enrichment processes. Then the extracted toxin went through SDS - PAGE for its toxin protein molecular weight to be identified. [ Result ] From the experiments, the abstracted toxin protein heavy chain was about 98 KDA and light chain about 53 KDA, which was consistent with molecular weight of type C botulinum toxin theory. [ Conclusion] What we have extracted is C - type Clostridium botulinum.

  13. Use of a Recombinant Fluorescent Substrate with Cleavage Sites for All Botulinum Neurotoxins in High-Throughput Screening of Natural Product Extracts for Inhibitors of Serotypes A, B, and E7

    Science.gov (United States)

    2007-12-14

    inhibitory molecules in the extracts, as exemplified by Fig. 4. Figure 4A shows the fractionation of Terminalia brownii root bark aque - ous extract (Table...from toxins. CRC Press, Boca Raton, FL. 31. Schmidt, J. J., and K. A. Bostian. 1997 . Endoproteinase activity of type A botulinum neurotoxin: substrate

  14. Mass Spectrometric Detection of Botulinum Neurotoxin by Measuring its Activity in Serum and Milk

    Science.gov (United States)

    Kalb, Suzanne R.; Pirkle, James L.; Barr, John R.

    Botulinum neurotoxins (BoNTs) are bacterial protein toxins which are considered likely agents for bioterrorism due to their extreme toxicity and high availability. A new mass spectrometry based assay called Endopep MS detects and defines the toxin serotype in clinical and food matrices via toxin activity upon a peptide substrate which mimics the toxin's natural target. Furthermore, the subtype of the toxin is differentiated by employing mass spectrometry based proteomic techniques on the same sample. The Endopep-MS assay selectively detects active BoNT and defines the serotype faster and with sensitivity greater than the mouse bioassay. One 96-well plate can be analyzed in under 7 h. On higher level or "hot" samples, the subtype can then be differentiated in less than 2 h with no need for DNA.

  15. Bacteria associated with processed crawfish and potential toxin production by Clostridium botulinum type E in vacuum-packaged and aerobically packaged crawfish tails.

    Science.gov (United States)

    Lyon, W J; Reddmann, C S

    2000-12-01

    Refrigerated vacuum-packaged storage has been shown to increase significantly the shelf life of fresh fish and seafood products, but the effect, if any, on the outgrowth and toxin production of Clostridium botulinum type E on cooked crawfish is unknown. Microflora associated with live crawfish reflect the microbial populations of the harvest water and sediments in which they are living. The presence or absence of specific pathogens in either vacuum-packaged or air-permeable bags of cooked crawfish have not been thoroughly evaluated. This study evaluates the potential survival and outgrowth of biological hazards in both vacuum-packaged and air-permeable-packaged cooked crawfish held at 4 and 10 degrees C for 30 days. During shelf-life studies of vacuum-packaged and air-permeable-bagged cooked crawfish, a total of 31 bacterial species were isolated and identified from crawfish samples using both selective and nonselective media. The only pathogens isolated from both vacuum-packed and air-permeable bags of processed crawfish samples during shelf-life studies were strains of Aeromonas hydrophila and Staphylococcus aureus. C. botulinum type E and Clostridium perfringens species were not isolated from any of the uninoculated crawfish samples. Cooked crawfish were inoculated with 10(3) C. botulinum type E spores per g of crawfish tail meat to determine whether cooked crawfish tails would support the growth of C. botulinum type E strains and produce toxin at refrigerated temperatures. Spore-inoculated crawfish tails were vacuum packaged in both a high barrier film and an air-permeable bag and stored at 4 degrees C and 10 degrees C for 30 days. C. botulinum toxin E was not detected in any of the spore-inoculated packages throughout the shelf-life study until day 30. Microbiological data from this study should be useful in the development and implementation of the hazard analysis and critical control point plans for processed crawfish tails.

  16. A型肉毒毒素在斜视治疗中的应用%Botulinum toxin A in treatmen of the strabismus

    Institute of Scientific and Technical Information of China (English)

    王贝贝; 胡依博; 王素萍(综述); 王瑞峰(审校)

    2016-01-01

    Botulinum toxin A injections the extraocular muscles which can cause temporary paralysis to change the positiong of eye in order to treatment of strabismus.And it can produce the extraocular muscle temporary weakness and permanent eye position change, with the advantages of repeated injections, simple operation and less side effects, etc. In this paper, botulinum toxin type A application in strabismus treatment were summarized.%肉毒毒素A型注射眼外肌可造成暂时性麻痹来改变眼位治疗斜视,可产生眼外肌暂时的无力和永久的眼位改变,并具有可重复注射,操作简单和副作用少等优点。本文对肉毒毒素A型在斜视治疗中的应用进行综述。

  17. What Clinical Strategies Are Applied for Botulinum Toxin Injection in the Oromandibular Region?

    DEFF Research Database (Denmark)

    Bakke, Merete; Dalager, Torben; Møller, Eigild

    2016-01-01

    Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from cholinergic nerve terminals in muscles or salivary glands. With reduced activation, the muscle activity or secretion decreases. Indications for medical, non‐cosmetic use of BoNT in the orofacial area include among others...... oromandibular dystonia, painful masseter hypertrophy, Frey's syndrome, and severe drooling. The chapter covers anamnestic characteristics of these conditions as well as clinical, electromyographic (EMG) and laboratory findings, treatment methods with guided injections, and outcome from systematic treatment...

  18. Usefulness of Magnetic Resonance Neurography for Diagnosis of Piriformis Muscle Syndrome and Verification of the Effect After Botulinum Toxin Type A Injection

    OpenAIRE

    Yang, Hea Eun; Park, Jung Hyun; Kim, Sungjun

    2015-01-01

    Abstract Piriformis muscle syndrome (PMS) is a controversial neuromuscular disorder that is presumed to involve compression neuropathy of the sciatic nerve at the level of the piriformis muscle. Botulinum toxin A (BTX-A) injection into the piriformis muscle is widely used as a treatment aimed at relieving sciatic nerve compression. In 2 patients with PMS, magnetic resonance neurography (MRN) was taken before and after BTX-A injection. The first MRN was performed as a diagnostic tool, and the ...

  19. Use of botulinum toxin in musculoskeletal pain [v2; ref status: indexed, http://f1000r.es/16j

    Directory of Open Access Journals (Sweden)

    Jasvinder A Singh

    2013-07-01

    Full Text Available Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed.

  20. Efficacy of intraarticular botulinum toxin A and intraarticular hyaluronate plus rehabilitation exercise in patients with unilateral ankle osteoarthritis: a randomized controlled trial

    OpenAIRE

    Sun, Shu-Fen; Hsu, Chien-Wei; Lin, Huey-Shyan; Chou, Yi-Jiun; Chen, Jun-Yang; Wang, Jue-Long

    2014-01-01

    Background There was an increasing requirement for novel treatments of osteoarthritis (OA). The aim was to compare the efficacy of intraarticular Botulinum toxin type A (BoNT-A) and intraarticular hyaluronate plus rehabilitation exercise in patients with ankle OA. Methods This was a prospective, randomized, assessor-blinded study with a 6-month follow-up period, conducted in the outpatient rehabilitation department at a university-affiliated tertiary care medical center. Seventy-five patients...

  1. 肉毒毒素引发一起食物中毒的检测%Detection of food poisoning caused by botulinum toxin

    Institute of Scientific and Technical Information of China (English)

    秦丽云; 李云; 王晓丽; 徐保红; 柳连顺; 吕国平

    2014-01-01

    目的 对因食入自制臭豆腐后,引起家庭内食物中毒的病因进行检测.方法 按中华人民共和国国家标准GB/T 4789·12-2003《食品卫生微生物学检验肉毒梭菌及肉毒毒素检验》方法,对食物中毒的样品用小白鼠进行肉毒毒素检测.结果 测定自制臭豆腐中存在B型肉毒毒素,毒力大致为1 000 ~ 10 000 MLD/ml的范围.结论 根据试验结果查明了中毒原因,为事故的调查提供了依据.%Objective The aim of this study was to investigate the cause of a food poisoning case in a family after consuming homemade stinky tofu.Methods The botulinum toxin was examined by mice virulence test according to GB/T 47890.12-2003 microbiological examination of food hygiene (examination of Clostridium botulinum and botulinum toxin).Results The type B botulinum toxin was identified in homemade stinky tofu,and the virulence of the toxin was approximately 1000-10000 MLD/g.Conclusion The cause of this food poisoning incidence was quickly identified by the test results,and the study provided the basis for investigating food poisoning.

  2. Simplified technique for injection of Botulinum Toxin to Obturator Internus muscle using ultrasound‐guided nerve stimulation for persistent pelvic pain

    OpenAIRE

    Evans, Susan Florence; Porter, Justin Matthew

    2015-01-01

    Botulinum toxin (BoNT) injections have been used to reduce muscle spasm in the presence of severe pelvic pain. However, while pubococcygeus is easily accessed vaginally, injection to obturator internus is more complex – with variation in operative technique and needle placement confounding the ability to assess outcomes. We describe a simplified technique for BoNT injection to obturator internus using neurostimulation under ultrasound guidance.

  3. [The results of single-event multilevel orthopedic surgeries and the early rehabilitation used in complex with botulinum toxin treatment in patients with spastic forms of cerebral palsy].

    Science.gov (United States)

    Popkov, D A; Zmanovskaya, V A; Gubina, E B; Leonchuk, S S; Butorina, M N; Pavlova, O L

    2015-01-01

    To evaluate motor possibilities of patients with children spastic palsy (CSP) one year after single-event multilevel orthopedic low extremity surgeries in combination with early rehabilitation treatment including botulinum toxin treatment. Authors studied the results of operative orthopedic treatment in 55 patients with CSP, aged from 5 to 17 years (mean 11.9 ± 2.5 years), who underwent multilevel surgeries with early functional rehabilitation using 1.5 treatment courses with 6-8 week treatment-free periods during 9-12 months in combination with a single injection of disport in the post-operative period. We performed 74 surgeries 140 episodes of botulinum toxin treatment using average doses of Botulinum toxin 10 U per kg of body mass injected into low extremity muscles. In the post-operative period, authors recorded a significant reduction in pain syndrome, assessed with a pain intensity scale, from 8.6 ± 1.2 to 4.3 ± 1.1 scores (p treatment in the post-operative period promotes the functional rehabilitation, increases rates of loading during training sessions and the motivation of CSP patients to restore the lost activity.

  4. AB204. Repeated intradetrusor botulinum toxin type A injections are still effective for patients with neurogenic detrusor overactivity secondary to spinal cord injury in China

    Science.gov (United States)

    Chen, Hui; Yang, Xinghua; Zeng, Jingwen; Huang, Maping; Liu, Qiuling; Huang, Jiebing; Huang, Tianhai; Xie, Keji; Jiang, Chonghe

    2016-01-01

    Objective To assess effective outcomes following repeated treatment with intradetrusor botulinum toxin type A in patients with neurogenic detrusor overactivity (NDO). Methods Patients with NDO secondary to spinal cord injury (SCI) were enrolled. Botulinum toxin type A 200 U detrusor injections by a rigid cystoscope were repeated. Primary outcomes were urodynamic variables including maximum detrusor pressure during first involuntary detrusor contraction (Pdetmax IDC) filling cystometry, detrusor compliance (DC). Secondary outcomes were improvement of the patient’s quality of life (QoL) measured by Incontinence-Specific Quality-of-Life Instrument (I-QoL), the validated short forms of Urogenital Distress Inventory (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7). Related adverse events were recorded. Results From 2012 to 2014, 159 injections were performed in 52 patients (44 male, 8 female). The mean age was 36.67 years. The maximum number of repeated injections was five. BC increased from (4.03–7.45) to (6.96–10.86) mL/cmH2O, Pdetmax in bladder storage decreased from (42.80–79.52) to (26.40–43.33) cmH2O, respectively. The I-QoL, UDI-6 and IIQ-7 showed a consistent improvement after repeated injections. Conclusions Repeated intradetrusor botulinum toxin type A injections remain improve QoL in patients with NDO secondary to SCI.

  5. Laboratory diagnosis of botulinum toxin E poisoning%一起E型肉毒毒素中毒的实验室诊断

    Institute of Scientific and Technical Information of China (English)

    焦焱; 汪春翔; 葛华; 来身德

    2011-01-01

    Objective To detect the botulinum toxin in poisoned food, in order to guide the emergency treatment Method According to the method of CB/T4789.12 - 2003, it was Food Hygiene Microbiology in Examination of Clostridium Botulinum and Botuliruis Toxin, selecting the samples from poisoned food, and than tested by toxicity test Results Botulinum toxin type E existed in poisoned food. Conclusions By the test, we can clear and definite the poisoning reason quickly and provided evidences for timely accurate treatment.%目的检测中毒食品中的肉毒毒素,以指导救治。方法按中华人民共和国国家标准GB/T4789. 12-2003(食品卫生微生物学检验肉毒梭菌及肉毒毒素检验),用采集的食物中毒样品对小白鼠进行毒力检测。结果中毒食品中检出E型肉毒毒素。结论根据试验结果很快查明中毒原因,为及时救治中毒患者提供了强有力的依据。

  6. ADP-ribosylation of actins in fibroblasts and myofibroblasts by botulinum C2 toxin: Influence on microfilament morphology and migratory behavior

    DEFF Research Database (Denmark)

    Rønnov-Jessen, Lone; Petersen, Ole William

    1996-01-01

    ., Petersen, O. W. J. Cell Biol. 1996, 134, 67-80). In the present study we have expanded on the functional significance of actin isotypes in fibroblasts from the opposite point of view, namely filamentous nonmuscle actin. Nonmuscle actins in fibroblasts and myofibroblasts were ADP-ribosylated by Clostridium...... botulinum C2 toxin. The substrate for C2 toxin is globular actin, which upon ribosylation cannot incorporate into microfilaments. The pattern of actin ADP-ribosylation in (myo)fibroblasts in the presence of [32P]NAD was analyzed by isoelectric focusing, fluorography and immunoblotting. The influence of C2...

  7. [Serotype identification and antibiotic susceptibility of Shiga toxin-producing Escherichia coli in the Weishan area in Shandong Province, China].

    Science.gov (United States)

    Shao, C C; Hu, B; Bi, Z W; Kou, Z Q; Fang, M; Chen, B L; Bi, Z Q

    2017-01-06

    Objective: To determine the serotypes and drug resistance profiles of Shiga toxin-producing Escherichia coli (STEC) in animal stools from the Weishan area in Shandong Province, China. To provide the basis for further study. Methods: Five hundred animal stool samples (from pigs, cattle, sheep, dogs and birds) were collected from the Weishan area and STEC strains were isolated from these samples. Strains were serotyped by a serum agglutination test, and their drug resistance profiles were determined through antimicrobial sensitivity experiments. In this study, PCR was used to detect tetracycline resistance genes (tetA, tetB, tetC, tetD) and beta-lactam resistance genes (blaSHV-1, blaCTX-M, blaTEM). Results: Sixteen strains of STEC were isolated from animal stool samples. Thirteen strains were isolated from pig stool samples, two from bovine stool samples and one from a sheep stool sample. Two of the strains were identified as E. coli O157:H7, and other 14 strains were non-O157 STEC of different serotypes. Antimicrobial sensitivity experiments showed that 15 of the strains were multidrug resistant. The rates of resistance were as follows: nalidixic acid (12/16 strains), sulfisoxazole (11/16), trimethoprim and sulphame-thoxazole (11/16), doxycycline (9/16), azithromycin (9/16), tetracycline (9/16), chloramphenicol (8/16) and streptomycin (8/16). Therefore, nalidixic acid showed the highest rate of resistance among the strains, followed by trimethoprim and sulphame-thoxazole, and sulfisoxazole. Resistance to cefepime or imipenem was not detected. In total, three types of drug resistance genes (tetA, tetB and tetC) were detected among the 16 strains. Conclusion: The results showed that STEC strains isolated from animals in the Weishan area were of a range of serotypes. The 16 strains of STEC isolated from animal stools in this area were resistant to a number of antibiotics, with many strains displaying multidrug resistance.

  8. Phospholipase C Produced by Clostridium botulinum Types C and D:Comparison of Gene, Enzymatic, and Biological Activities with Those of Clostridium perfringens Alpha-toxin

    Directory of Open Access Journals (Sweden)

    Sakurai,Jun

    2013-02-01

    Full Text Available Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs, the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  9. Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers: a double-blind, randomized, dose-ranging study.

    Science.gov (United States)

    Wohlfarth, K; Schwandt, I; Wegner, F; Jürgens, T; Gelbrich, G; Wagner, A; Bogdahn, U; Schulte-Mattler, W

    2008-12-01

    Despite extensive clinical experience and published data regarding botulinum toxin, questions remain about the clinical substitution of one botulinum toxin formulation for another. In the case of Dysport and Botox, dose-equivalence ratios ranging from 1:1 to 6:1 (Dysport:Botox) have been advocated. This dose-ranging, electroneurographic study investigated the dose equivalence, diffusion characteristics (spread) and safety of these two type-A toxins in 79 volunteers. Dysport and Botox caused significant and similar reductions in compound muscle action potential (CMAP) amplitude in the target muscle (extensor digitorum brevis, EDB) 2 weeks after injection, with effects persisting to the 12-week timepoint. For both products, the reduction in amplitude was increased with increasing doses and with increasing concentration. The effects of toxin on neighbouring muscles were much smaller and of a shorter duration than those on the target muscle, implying a modest spread of toxin. Unlike the target muscle, the effects were greater with the higher volume, suggesting this volume led to greater diffusion from the EDB. No adverse events were reported. Statistical modelling with CMAP amplitude data from the target muscle gave a bioequivalence of 1.57 units of Dysport:1 unit of Botox (95 % CI: 0.77-3.20 units). The data indicate that a dose-equivalence ratio of 3:1 was within the statistical error limits, but ratios over 3:1 are too high.

  10. Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

    Science.gov (United States)

    Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

    2013-01-01

    Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  11. Comparative Study of Efficacy and Safety of Botulinum Toxin a Injections and Subcutaneous Curettage in the Treatment of Axillary Hyperhidrosis.

    Science.gov (United States)

    Budamakuntla, Leelavathy; Loganathan, Eswari; George, Anju; Revanth, B N; Sankeerth, V; Sarvjnamurthy, Sacchidananda Aradhya

    2017-01-01

    Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3(rd) and 6(th) month after the procedure. At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events.

  12. Studies on growth and toxin production of C. botulinum type E on cod homogenate treated with a combination of spices, sodium chloride and gamma-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, A.K. (Atomic Energy Centre, Dacca (Bangladesh)); Ando, Y.; Karashimada, T.; Kameyama, K.

    1979-09-01

    Cod homogenates inoculated with spores of C. botulinum type E strain Erimo at 10/sup 2/ and 10/sup 4//g were treated with 1% and 2% sodium chloride, 0.25% each of mustard, garlic and turmeric and 0.3 Mrad ..gamma..-radiation either in single or combination treatments. The growth and toxin production of type E spores in the inoculated homogenates were followed at incubation temperatures of 30/sup 0/, 10/sup 0/ and 5/sup 0/C for 7, 28 and 56 days respectively. Growth and gas formation were noted in all the samples but type E toxin could not be detected. The reason for the absence of toxin in both the untreated and treated homogenates could not be ascertained. Inadequate detection method, unfavourable growth conditions in the homogenate and weak toxigenicity of the strain employed have been advanced as probable factors that contributed to the negative results on the toxin assay.

  13. Multidisciplinary rehabilitation following botulinum toxin and other focal intramuscular treatment for post-stroke spasticity.

    Science.gov (United States)

    Demetrios, Marina; Khan, Fary; Turner-Stokes, Lynne; Brand, Caroline; McSweeney, Shane

    2013-06-05

    Spasticity may affect stroke survivors by contributing to activity limitations, caregiver burden, pain and reduced quality of life (QoL). Spasticity management guidelines recommend multidisciplinary (MD) rehabilitation programmes following botulinum toxin (BoNT) treatment for post-stroke spasticity. However, the evidence base for the effectiveness of MD rehabilitation is unclear. To assess the effectiveness of MD rehabilitation, following BoNT and other focal intramuscular treatments such as phenol, in improving activity limitations and other outcomes in adults and children with post-stroke spasticity. To explore what settings, types and intensities of rehabilitation programmes are effective. We searched the Cochrane Stroke Group Trials Register (February 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 12), MEDLINE (1948 to December 2011), EMBASE (1980 to January 2012), CINAHL (1982 to January 2012), AMED (1985 to January 2012), LILACS (1982 to September 2012), PEDro, REHABDATA and OpenGrey (September 2012). In an effort to identify further published, unpublished and ongoing trials we searched trials registries and reference lists, handsearched journals and contacted authors. We included randomised controlled trials (RCTs) that compared MD rehabilitation (delivered by two or more disciplines in conjunction with medical input) following BoNT and other focal intramuscular treatments for post-stroke spasticity with placebo, routinely available local services, or lower levels of intervention; or studies that compared MD rehabilitation in different settings, of different types, or at different levels of intensity. We excluded RCTs that assessed the effectiveness of unidisciplinary therapy (for example physiotherapy only) or a single modality (for example stretching, casting, electrical stimulation or splinting only). The primary outcomes were validated measures of activity level (active and passive function

  14. Therapeutic Approaches for Botulinum Intoxication Targeting Degradation of the Light Chain

    Science.gov (United States)

    2013-04-01

    Synaptic Research will develop dichain hybrids consisting of Clostridium botulinum toxin light chains (LCs) from serotypes A (long-lived) and E...provided this plasmid to the McNutt laboratory that will use a modified version of this virus to produce transgenic mice expressing the designer...interactions via FRET using 24 transgenic lines that co-express fluorescently tagged LCs and target proteins. After optimization of pull-down

  15. Botulinum toxin in the management of chronic migraine: clinical evidence and experience.

    Science.gov (United States)

    Escher, Claus M; Paracka, Lejla; Dressler, Dirk; Kollewe, Katja

    2017-02-01

    Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox(®)) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM.

  16. Efecto protector de la toxina botulínica en colgajos cutáneos The protective effect of botulinum toxin on skin flaps

    Directory of Open Access Journals (Sweden)

    C.X. Astudillo Carrera

    2011-06-01

    Full Text Available Los colgajos cutáneos de patrón vascular randomizado son de gran utilidad en Cirugía Reconstructiva; un aporte vascular adecuado es el factor más importante para la supervivencia de los mismos. Realizamos un estudio experimental levantando un total de 36 colgajos en el dorso de 9 conejos (4 en cada conejo: a 9 controles, b 9 con aplicación de toxina botulínica tipo A transoperatoria a lo largo del colgajo, c 9 con toxina botulínica tipo A aplicada 7 días antes del procedimiento quirúrgico, y, d 9 con aplicación de toxina botulínica tipo A transoperatoria más epinefrina. El análisis de los colgajos se realizó a través de imágenes digitales que se examinaron con el programa ImageJ. Efectuamos el análisis estadístico con la prueba T de Student. La evaluación final de los colgajos se realizó al séptimo día, tiempo en el cual se obtuvo: a una media de área necrótica en los controles del 72.17 ± 3.9% ; b en los que se aplicó toxina botulínica transoperatoria el porcentaje de aérea necrótica fue del 5.09 ± 1.2% p = 0.032; c en aquellos en los que la toxina botulínica se aplicó 7 días antes del procedimiento se reportó necrosis del 24.97 ± 2.7% p = 0.041 y d en los que se aplicó toxina botulínica transoperatoria más epinefrina el porcentaje de necrosis fue del 23.90 ± 3.9% p = 0.045. Concluimos que la toxina botulínica tipo A actúa como protector contra el proceso de sufrimiento-isquemia de los tejidos, debido a su acción vasodilatadora, recomendando su aplicación al inicio del procedimiento quirúrgico.Random-pattern cutaneous flaps are very useful in Reconstructive Surgery; an adequate vascular contribution is an important factor for the survival of the flaps. We designed an experimental study elevating a total of 36 dorsal flaps, divided in 4 groups: a 9 were controls, to which 0.9% physiological solution was applied, b 9 with a transoperatory application of type A botulinum toxin throughout the length of

  17. Individual and bivalent vaccines against botulinum neurotoxin serotypes A and B using DNA-based Semliki Forest virus vectors.

    Science.gov (United States)

    Yu, Yunzhou; Yu, Jiyu; Li, Na; Wang, Shuang; Yu, Weiyuan; Sun, Zhiwei

    2009-10-19

    We evaluated individual and bivalent replicon vaccines against Clostridiumbotulinum neurotoxin serotypes A (BoNT/A) or B (BoNT/B). The DNA replicon vaccine (pSCARSBHc) encoding the Hc domain of BoNT/B (BHc) induced better responses and protection against BoNT/B mouse challenge than conventional DNA vaccine. The dual-expressing DNA vaccine (pSCARSA/BHc) protected similarly to a DNA replicon vaccine mixture (pSCARSAHc+pSCARSBHc). Additionally, recombinant SFV particles, VRP-AHc or VRP-BHc, protected mice from high-dose BoNT/A or BoNT/B challenge, respectively. Mice given either dual-expressing VRP-A/BHc or mixture of VRP-AHc and VRP-BHc were protected from challenge with serotype A/B mixtures. These data justify further testing in other animals or humans.

  18. High-level expression, purification, crystallization and preliminary X-ray crystallographic studies of the receptor binding domain of botulinum neurotoxin serotype D

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Gao, Xiaoli; Qin, Lin; Buchko, Garry W.; Robinson, Howard; Varnum, Susan M.

    2010-12-01

    Botulinum neurotoxins (BoNTs) are highly toxic proteins for humans and can cause neuroparalytic disease botulism. Due to the limitations of production and manipulation of holoenzymes, expressing non-toxic heavy chain receptor binding domains (HCR) has become a common strategy for vaccine and antibody development. Meanwhile, large quantities and highly purified soluble proteins are required for research areas such as antibody maturation and structural biology. We present high level expression and purification of the BoNT serotype D HCR in E. coli using a codon-optimized cDNA. By varying expression conditions, especially at low temperature, the protein was expressed at a high level with high solubility. About 150-200 mg protein was purified to >90% purity from 1 L cell culture. The recombinant D_HCR was crystallized and the crystals diffracted to 1.65 Å resolution. The crystals belong to space group P212121 with unit cell dimensions a = 60.8 Å, b = 89.7 Å, c = 93.9 Å. Preliminary crystallographic data analysis revealed one molecule in asymmetric unit.

  19. Identification of fibroblast growth factor receptor 3 (FGFR3 as a protein receptor for botulinum neurotoxin serotype A (BoNT/A.

    Directory of Open Access Journals (Sweden)

    Birgitte P S Jacky

    Full Text Available Botulinum neurotoxin serotype A (BoNT/A causes transient muscle paralysis by entering motor nerve terminals (MNTs where it cleaves the SNARE protein Synaptosomal-associated protein 25 (SNAP25206 to yield SNAP25197. Cleavage of SNAP25 results in blockage of synaptic vesicle fusion and inhibition of the release of acetylcholine. The specific uptake of BoNT/A into pre-synaptic nerve terminals is a tightly controlled multistep process, involving a combination of high and low affinity receptors. Interestingly, the C-terminal binding domain region of BoNT/A, HC/A, is homologous to fibroblast growth factors (FGFs, making it a possible ligand for Fibroblast Growth Factor Receptors (FGFRs. Here we present data supporting the identification of Fibroblast Growth Factor Receptor 3 (FGFR3 as a high affinity receptor for BoNT/A in neuronal cells. HC/A binds with high affinity to the two extra-cellular loops of FGFR3 and acts similar to an agonist ligand for FGFR3, resulting in phosphorylation of the receptor. Native ligands for FGFR3; FGF1, FGF2, and FGF9 compete for binding to FGFR3 and block BoNT/A cellular uptake. These findings show that FGFR3 plays a pivotal role in the specific uptake of BoNT/A across the cell membrane being part of a larger receptor complex involving ganglioside- and protein-protein interactions.

  20. Identification of fibroblast growth factor receptor 3 (FGFR3 as a protein receptor for botulinum neurotoxin serotype A (BoNT/A.

    Directory of Open Access Journals (Sweden)

    Birgitte P S Jacky

    Full Text Available Botulinum neurotoxin serotype A (BoNT/A causes transient muscle paralysis by entering motor nerve terminals (MNTs where it cleaves the SNARE protein Synaptosomal-associated protein 25 (SNAP25206 to yield SNAP25197. Cleavage of SNAP25 results in blockage of synaptic vesicle fusion and inhibition of the release of acetylcholine. The specific uptake of BoNT/A into pre-synaptic nerve terminals is a tightly controlled multistep process, involving a combination of high and low affinity receptors. Interestingly, the C-terminal binding domain region of BoNT/A, HC/A, is homologous to fibroblast growth factors (FGFs, making it a possible ligand for Fibroblast Growth Factor Receptors (FGFRs. Here we present data supporting the identification of Fibroblast Growth Factor Receptor 3 (FGFR3 as a high affinity receptor for BoNT/A in neuronal cells. HC/A binds with high affinity to the two extra-cellular loops of FGFR3 and acts similar to an agonist ligand for FGFR3, resulting in phosphorylation of the receptor. Native ligands for FGFR3; FGF1, FGF2, and FGF9 compete for binding to FGFR3 and block BoNT/A cellular uptake. These findings show that FGFR3 plays a pivotal role in the specific uptake of BoNT/A across the cell membrane being part of a larger receptor complex involving ganglioside- and protein-protein interactions.